Indocyanine green test

Prerequisites for correct laboratory findings 91 9.2 Indocyanine green test (ICG) 108... 

Caesar J, Shaldon S, Chiandussi L, et al. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 1961 21 43-57. 

Several tests have been developed to quantify actual liver function, including indocyanine green (ICG), aminopyrine and bromosulpho-thalein. The principle of these tests is to determine whether hepatic blood flow or cell function is reduced by administering a chemical which is exclusively taken up or metabolised by the liver. For example, in the ICG clearance test the ICG is a non-toxic chemical solely taken... 

Clemmesen JO, Tygstrup N, Ott P (1998) Hepatic plasma flow estimated according to Pick s principle in patients with hepatic encephalopathy evaluation of indocyanine green and D-sorbitol as test substances. Hepatology 27 . 666-673. 

DIAGNOSTIC TESTS FOR RETINAL DISEASE INDOCYANINE GREEN ANGIOGRAPHY ... 

FIGURE 7.4 Relationship between Child-Pugh stages of liver disease severity and extent of impairment in antipyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance, and indocyanine green clearance (ICG). (Adapted from data published by Herold C, Heinz R, Niedobitek G et al. Liver 2001 21 260-5.)... 

Indocyanine green was introduced by J. Caesar et al. in 1961 as a liver function test. Anionic tricarbocyanine dye is referred to as an ideal test substance (1.) it is tolerated very well there have been no reports of any incidents so far, and even paravenous injection is tolerated (2.) it is excreted unchanged by hepatocytes in the bile as there is no bio transformation - this is why ICG clearance is valid as a measure of hepatocellular uptake and transport processes (3.) there is no interference with drugs (except rifamycin), haemolysis, bilirubin (up to approx. 4 mg/dl) or hyperlipidaemia (4.) the substance is not subject to the enterohepatic circulation (J.) the rapid elimination, which depends on hepatic perfusion ( flow-limited ), allows the calculation of the hepatic flow volume as a whole based on ICG clearance (6.) the method is simple to perform. 

The compensated stage does not usually display any signs of liver insufficiency (except possibly jaundice), nor are there any typical ailments. Functional parameters that can be quantified in routine laboratory tests (such as cholinesterase, albumin. Quick s value, bile acids) may still be normal or only minimally impaired in the individual instance. In contrast, liver tolerance tests (galactose, indocyanine green, etc.) demonstrate a reduction of liver function which is already quite considerable. 

Xenobiotics are foreign substances that are cleared and metabolized by the liver and some have been used as tests of liver function. For example, certain Hpophilic substances such as bromsulfophthalein (BSP), indocyanine green (ICG), aminopyrine, caffeine, Udocaine, and rose Bengal are excreted into bile as the intact parent compound, its conjugates, or both. The clearance of these xenobiotics by the liver is normally very rapid, and it is beUeved that uptake by hepa-... 

Methods that involve studying the disposition of some exogenously administered agent (e.g. indocyanine green, antipyrine, galactose or dextromethorphan) have now been superceded by functional (often multicomponent) tests. Mono-ethylglycinexylidide formation has not found wide acceptance. More complicated Cox proportional hazards models may exist for other liver diseases, but are only used specifically for them (e.g. the Mayo Clinic Survival Model for primary biliary cirrhosis see the US FDA Guidance). 

In general, tests with these dyes were found to be less suitable than tests using BSP or rose bengal because of (a) toxicity (R15), (b) apparent insensitivity to liver dysfunction, or (c) extrahepatic uptake. Only indocyanine green (Cl6, H27), a tricarbocyanine dye used initially for blood flow studies (F5), has shown any promise as an alternative to BSP or rose bengal. 

An indocyanine green retention test similar to the BSP retention test (C16) gave a mean retention value in health of 3.9%, 20 minutes after a... 

There are conflicting reports, however, of the relative sensitivities of different tests in the recovery phase. One group of patients tended to retain abnormal flocculation reactions and elevated 1-minute serum bilirubin values longer than abnormal BSP values (N5). Other investigators have found decreased BSP removal rates in patients who had had infective hepatitis but who no longer showed other clinical or biochemical evidence of the disease (II, D7, W32). Abnormal BSP retention persists for longer than abnormal indocyanine green disposal (L5). 

The majority of investigations in patients have involved measurement of dye retention only. The retention test, at least with BSP, fails to take into account the shape of the plasma decay curve. Thus, in some patients the plasma dye concentration falls more slowly than normal during the initial phase but still reaches a normal level at 45 minutes. The plasma disappearance curve of indocyanine green more closely approximates a single-phase exponential curve during the period of the test, and if it was considered desirable to collect only one sample it would be preferable to use indocyanine green. The optimal dose of dye to be administered in a retention test cannot be defined until further comparative studies have been done. It would be sensible meanwhile to use the standard dose (5 mg/kg) if only to obtain results comparable with the majority of those obtained during the past 20 years. 

Hepner GW, Vesell E, Lipton A, Harvey HA, Wilkinson GR, Schenker Disposition of aminopyrine, anti tyrine, diazepam, and indocyanine green in patients with liver disease or on anticcxivulsant theraity diazepam Ix eath test and correlations in drug elimination JD76 Clin Med ( 977) 90,440-56... 

Clearance tests of liver function assess a number of physiologic activities including hepatic uptake, hepatic metabolism, and hepatic excretion. Typical clearance tests of liver function include indocyanine green (ICG), antipyrine clearance test and C aminopyrine breath test. These tests give an estimation of the ability of the liver to extract and detoxify exogenous toxins (xenobiotics). Measuring the excretion of endogenously produced serum bile acids is an additional measure of hepatic clearance and has been used as a sensitive measure of early solvent hepatotoxicity." "... 

Ohe et al. [67] reported the synthesis of ROMP block copolymers containing a tumor-imaging agent for in vivo testing in mice. Amphiphilic triblock copolymers bearing the indocyanine green moiety were prepared by a combination of ROMP of norbornadiene (NBD) derivatives, Cu-catalyzed [2-l-3]-dipolar click reaction. 

In our work we utilized the long-wavelength dye indocyanine green (ICG) (Figure 24), which is widely used in a variety of in vivo medical applications. ICG is not toxic and is approved by the U.S. Food and Drug Administration for use in humans, typically by injection. ICG displays a low quantum yield in solution, 0.016, and a somewhat higher quantum yield when bound to serum albumin. Albumin adsorbs to form a monolayer and ICG spontaneously binds to albumin. ICG is chemically and photochemically unstable, and thus provided us with an ideal opportunity to test deposited silver for both metal-enhanced emission and increased ICG photochemical stability. 

---