Nuclear Medicine
CLINICAL DECISION SUPPORT
The Mebrofenin derivative is the most widely used due to higher hepatic extraction and better performance in patients with hepatic dysfunction.
[99mTc]Tc-HIDA compounds are extracted from the circulation by hepatocytes using a mechanism similar to other organic amines. Unlike bilirubin, these compounds are secreted into the biliary canaculi without conjugation. These characteristics of [99mTc]Tc-HIDA compounds can be utilized to demonstrate the distribution of functioning hepatic tissue, illustrate the formation and secretion of bile, and follow the passage of bile through the biliary tree, gallbladder, and small intestine.
HIDA scintigraphy can provide functional information about the hepatobiliary system in several important clinical settings:
In recent years, there has been a clinical re-alignment in the use of HIDA scintigraphy with the widespread availability of ultrasound and cross-sectional imaging. Consequently, it is rare these days to utilize [99mTc]Tc-HIDA compounds to diagnose acute cholecystitis, for example, although the accuracy in this setting for HIDA scintigraphy has been shown to be in the region of 90-95% [104].
In the evaluation of functional biliary syndromes (e.g. biliary dyskinesia and SOD), the Rome IV criteria (2016) advocate the use of HIDA scintigraphy in those individuals in whom there is a moderate clinical suspicion of biliary dyskinesia, which persists after negative conventional investigations to exclude structural problems such as gallstones [105].
There are no high-quality randomized trials to demonstrate the efficacy of HIDA scintigraphy to determine which of these patients should proceed to cholecystectomy. However, observational studies show that up to 95% of patients selected on the basis of an abnormal GBEF on HIDA scintigraphy show sustained symptomatic improvement after cholecystectomy, and this is supported by consensus guidelines [106].
For adults, the recommended administered activity ranges from 111-185 MBq with the higher activities considered in patients with hyperbilirubinemia.
In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity to administer is 20 MBq.
The range of the effective doses for the suggested activities is 1.8-3.0 mSv.
Th Caveat
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
In normal subjects, [99mTc]Tc-HIDA compounds are taken up immediately by the hepatic parenchyma with rapid clearance of the mediastinal blood pool. The radiopharmaceutical is then secreted into the biliary tree, and the major hepatic ducts and common duct are visualized first. The gallbladder begins to fill by 10 min and is usually filled by 30-40 min, although up to 60 min is usually allowed. Approximately one-third of the bile enters the gallbladder, and the remaining two-thirds bypasses the gallbladder and enters the duodenum. Normal visualization of activity within the duodenum and proximal small intestine should occur by 1 h.
Non-visualization of the gallbladder, outside of the context of acute cholecystitis, could occur due to inadequate or prolonged fasting (<2 h or >24 h), hyperalimentation (e.g. total parenteral nutrition), severe hepatocellular dysfunction, severe intercurrent illness, and post-cholecystectomy.
Quantification of the GBEF is mandatory in evaluating for suspected biliary dyskinesia. A GBEF of >40% is usually considered normal, although slight variations in the normal cut-off can be seen depending on the method used to provoke gallbladder emptying. A ‘false-positive’ result, i.e., low GBEF in the absence of biliary dyskinesia, can be seen in conditions such as obesity, diabetes, and with certain drug therapy (e.g. calcium channel blockers and oral contraceptives), all of which might be associated with poor gallbladder emptying in the absence of biliary symptoms.
Several scintigraphic variables are used to detect SOD, including delayed biliary clearance from the bile ducts into the small bowel (liver hilum to duodenum transit time >10 min), delayed entry of tracer into bowel from time of injection (>30-60 min), and failure of drainage to accelerate after sincalide administration.
Patients with an intact gallbladder must fast 2-6 h prior to the examination to ensure that the gallbladder is not contracted and to encourage gallbladder filling. Morphine augmentation (with 0.04 mg/kg morphine sulphate administered intravenously over 2-5 min) is an accepted modification in cases of gallbladder non-visualization and can also be useful in the evaluation of suspected SOD. In order to stimulate gallbladder emptying and allow estimation of GBEF, sincalide (Kinevac®, Bracco Diagnostics), a C-terminal octapeptide synthetic analogue of cholecystokinin (CCK), is administered by slow i.v. injection (over at least 5 min but ideally as a 45-60 min infusion) at a dose of 0.02 mg/kg. Alternatively, a standardized lactose-free fatty meal may be given. Some studies show that proprietary long-chain triglyceride emulsions administered orally (e.g. Calogen 200 mL, Nutricia) may be used to stimulate gallbladder emptying in a reproducible and physiological manner [107]. Prolonged parenteral nutrition may produce false-negative studies in the setting of biliary atresia
Standardized protocols for HIDA scintigraphy should be available within every nuclear medicine department based on consensus guidelines [108].
A usual protocol would include data acquisition using a low energy, high-resolution collimator on a 128x128 matrix with initial image acquisition performed dynamically whenever possible from the time of injection to 60 min. Delayed images at 2 and 4 h are obtained in cases of suspected cholecystitis and non-visualization of the gallbladder. Anterior or right anterior oblique views are taken to include the liver and duodenum with additional views as needed. In post-operative imaging, it is important to tailor the study to individual patients taking account of the type of surgery performed. Delayed acquisitions (up to 24 h) with additional views (e.g. lateral or decubitus) are routinely obtained to demonstrate delayed bile drainage and to exclude small bile leaks or fistulae. Drainage catheters and bags should be included in the field of view as tracer uptake within these may be the only sign of a biliary leak. Hybrid imaging using a single photon-emission computed tomography/ computed tomography (SPECT/CT) camera can also improve the diagnostic confidence and specificity of the technique.