Gallstones top to toe: what the radiologist needs to know

Gallstones are solid rounded particles composed of a combination of cholesterol and bilirubin that form within the gallbladder and within the biliary system. The size and number of gallstones is variable with some patients forming multiple small gallstones and others forming single or few large stones.

The incidence of gallstones is increasing in Western populations as obesity levels rise. In the USA, 8.6% of Caucasian men and 16.6% of women have gallstones [1]. The vast majority of gallstones are asymptomatic and require no follow-up; however, approximately 10–15% of gallstones will become symptomatic over a period of 10–15 years of follow-up [2, 3]. The symptomatic manifestations of gallstones are variable and range from mild symptoms such as biliary colic to severe acute presentations such as pancreatitis, which can be associated with significant morbidity and mortality. In a patient that has suffered a symptomatic manifestation of gallstones, the incidence of a further manifestation over their lifetime is approximately 3% per year [2]. The risk for gallstone-related pathology is also related to the number and size of stones with numerous larger stones more likely to cause symptoms. For this reason, it is suggested that once symptoms present, the patient should be offered a cholecystectomy [3‐5].

The main risk factors for gallstone formation are outlined in Table 1, and the factors protective against gallstones are outlined in Table 2.

There are three main types of gallstones: cholesterol, mixed and pigmented. Cholesterol gallstones account for 10% of gallstones and are composed of at least 50% cholesterol and form with supersaturation of bile. Patients with high-fat diets and high serum lipids are more likely to have a higher cholesterol composition. Pigmented gallstones, which are darker in colour and are composed mainly of bilirubin with < 20% cholesterol, form with supersaturation of unconjugated bilirubin. There are two subtypes of pigmented gallstones: black pigmented gallstones which are formed due to chronic haemolysis, cirrhosis or intestinal malabsorption, and brown pigmented gallstones which are formed secondary to bacterial and parasitic infections such as Clonorchis sinensis or due to stasis of bile. Finally, mixed gallstones account for 80% of gallstones and have a cholesterol content of 20–50% [6, 7].

Multiple imaging modalities play a role in the diagnosis of the broad spectrum of gallstone-related disease including plain radiography, ultrasonography, computed tomography (CT), scintigraphy and magnetic resonance imaging (MRI).

Ultrasound is by far the most common and useful imaging modality in assessing gallstones within the gallbladder (cholelithiasis) and associated gallbladder pathology and has the added benefit of no radiation dose to the patient. With ultrasound, gallstones are characteristically echogenic and demonstrate posterior acoustic shadowing regardless of the gallstone composition (Fig. 1). As ultrasound is a bedside dynamic study, stone mobility can be demonstrated with patient manoeuvering, and this can help in differentiating gallstones from gallbladder polyps, which can mimic cholelithiasis sonographically.

Another principle advantage of ultrasound over other imaging techniques in the investigation of acute cholecystitis is the ability to evaluate for a sonographic Murphy’s sign, which can be a reliable indicator of acute cholecystitis with a high sensitivity [8]. Sonographic Murphy’s sign is where the patient reports maximal pain as the sonographer presses over the fundus of the distended gallbladder with the ultrasound probe (and differs to clinical Murphy’s sign).

The major limitation of ultrasound in the imaging of gallstone-related disease is the frequent inability to assess the distal common bile duct (CBD) due to overlying bowel gas. Occasionally, a stone can be seen within the biliary system; however, often the presence of a CBD stone can be inferred from visualised proximal biliary dilatation and clinical presentation with painful jaundice or an obstructive pattern on liver function tests. This requires further work up with alternative imaging.

Plain radiography is limited in the diagnosis of gallstones as only 15–20% of gallstones are radio-opaque on X-ray [6]. The classical radiographic appearance is the “Mercedes Benz sign” which is an outer radio-opaque rim with a radiolucent centre which is caused by calcification of the gallstone rim and gas fissuring within the gallstone. Calcification of gallstones occurs with increased calcium in bile [9] (Fig. 2).

On CT, a high percentage of cholesterol stones are hypoattenuating relative to bile (Fig. 3) and calcified stones are hyperattenuating relative to bile (Fig. 4); however, a significant proportion of stones are iso-attenuating relative to surrounding bile and may be radiologically occult on CT. Dual-energy CT has been shown to improve detection of gallstones with low KV imaging and base substance imaging, such as calcium-based and lipid-based imaging, which is more sensitive at detecting gallstones than traditional higher KV imaging. Despite these imaging advances, CT remains inferior to ultrasound at assessing the gallbladder and results in a significant radiation dose to the patient. As such, ultrasound is the imaging modality of choice for initial assessment of suspected gallbladder pathology. CT however can be very effective at assessing extra-biliary gallstone pathology and complications arising from gallstone pancreatitis and cholecystitis [8, 10].

MRI is another very effective tool for diagnosing gallstones and associated pathological processes. Magnetic resonance cholangiopancreatography (MRCP) is typically performed using heavily T2-weighted sequences, supplemented by fat-saturated T1- and T2-weighted MRI, and with steady-state gradient-echo acquisitions. Heavily T2-weighted image sequences are particularly helpful in delineating ductal anatomy. Gallstones typically appear as low signal or signal void on T2-weighted imaging surrounded by T2 hyperintense bile [11] (Fig. 5). MRCP has largely replaced endoscopic retrograde cholangiopancreatography (ERCP) as the gold standard for diagnosing choledocholithiasis due to its high sensitivity of 90–94% and specificity of 95–99% without the use of ionising radiation or ERCP-related complications such as pancreatitis which can result in significant morbidity and even mortality [12, 13].

Nuclear medicine imaging with scintigraphy and with SPECT/CT can be used to dynamically assess the gallbladder. Technicium-99 labeled mebrofenin is administered and taken up by bile producing cells and subsequently excreted into the biliary system. The patient is typically imaged at 1 h and at 4 h post-administration of radioisotope. A normal gallbladder will be well delineated as it fills with radioactive bile. In cases of cholecystitis or gallbladder obstruction due to an impacted stone in the cystic duct, the gallbladder will not be visualised as the radioactive will not accumulate within the gallbladder. If the gallbladder is not visualised, morphine analogues can be given to induce sphincter of Oddi contraction and aid gallbladder filling. Cholescintigraphy for acute cholecystitis has a sensitivity of 97% and a specificity of 94% [14]. This is actually superior to ultrasound; however, this technique is more expensive and time consuming and also confers a radiation dose to the patient and staff and thus is generally not a first-line investigation (Fig. 6).

There is an increasing role for interventional radiology (IR) in gallstone-related diseases. Percutaneous cholecystostomy can be used as a temporizing measure in critically ill patients who are too sick to proceed to immediate surgery and cholecystectomy. It is also occasionally being used as a therapeutic measure in the setting of an ageing population with multiple co-morbidities, many of whom may have contraindications to general anaesthesia and surgical intervention. In patients who have had a cholecystostomy placed, cholangiograms can be performed to demonstrate resolution of or ongoing obstruction of the biliary tree by assessing for filling defects (gallstones) within the biliary system (Fig. 7). Percutaneous transhepatic cholangiography (PTC) with biliary stenting is a very effective treatment to decompress the biliary system in the case of obstructing choledocholithiasis, most often in cases not amenable to ERCP. IR also play an active role in the management of the complications of gallstone disease through drain insertion for hepatic or peripancreatic abscesses, in the case of pancreatitis, and for post-operative intra-abdominal collections post-cholecystectomy.

The broad spectrum of gallstone-related disease can be broken down based on the anatomical locations in which they occur (Fig. 8).

Radiologists should be familiar with the wide range of pathological processes that can be seen secondary to gallstones in order to aid prompt diagnosis, treatment and intervention

It is hoped that through understanding the role of multimodality imaging and understanding the anatomic locations of the manifestations of gallstone-related disease, this review paper will assist the radiologist in diagnosing common and less common manifestations of gallstone-related pathology.