Primary Sclerosing Cholangitis Imaging
Primary sclerosing cholangitis (PSC) is a chronic, progressive, inflammatory disease characterized by fibrosis of the bile ducts. The cause is unknown, but a hypersensitivity reaction is implicated. Patients present with abnormalities of liver function tests and progressive intermittent obstructive jaundice, which may be associated with fever chills, night sweats, pain, and itching. The antimitochondrial antibody is present in about 95% of cases.  A liver biopsy, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP) can help achieve diagnosis. [2, 3, 4, 5]
Approximately 75% of patients with PSC have inflammatory bowel disease (IBD), primarily ulcerative colitis. Median survival of patients who do not receive a liver transplant is 12-15 years after diagnosis. 
Prevalence of PSC is 0 to 16.2 /100,000 persons and usually occurs in young and middle-aged men, with typical age at onset of 30-40 years. 
(The radiologic characteristics of PSC are demonstrated in the images below.)
The American Association for the Study of Liver Diseases and the European Association of the Study of the Liver have both recommended magnetic resonance cholangiopancreatography (MRCP) as the first-line modality for imaging bile duct abnormalities in PSC. The advantages of MRCP are that it is noninvasive and does not require contrast media or ionizing radiation. However, MRCP may have limited accuracy in early PSC.  Therefore, ERCP remains the mainstay for accurate diagnosis of ERCP through analysis of the hepatobiliary tree because of its higher sensitivity.  When there is still clinical suspicion with negative or nondiagnostic findings on MRCP, ERCP should be performed. ERCP can also be used for therapy with balloon dilatation or stenting. [13, 14, 15, 16, 17, 18, 19, 20, 21, 6]
ERCP is invasive and can potentially cause ascending cholangitis. 
Ultrasonography (US) is the initial examination modality of choice in patients presenting with jaundice and right upper quadrant pain. The liver may demonstrate nonspecific abnormalities on US, which infrequently leads to definitive diagnosis. The primary role of US is in helping clinicians make the diagnosis of other bile duct mechanical obstructions, such as gallstones and neoplasia.  Endoscopic ultrasound may be used for diagnosing extrahepatic PSC. 
Computed tomography (CT) scans also demonstrate nonspecific changes. Indistinguishable features may occur with cholangiocarcinoma and other forms of cholangitis. Intra-abdominal lymphadenopathy, suggesting cholangiocarcinoma, may be detected by CT. 
Plain radiographs have little role to play in the diagnosis of PSC. MRCP and ERCP are the preferred modalities because of their high sensitivity and specificity. ERCP is considered the gold standard, with a specificity of approximately 96%. Typical cholangiographic findings include multifocal annular biliary structures with dilated intrahepatic and extrahepatic bile ducts and alternating normal segments. This is known as the beaded pattern of PSC. 
(See the images below.)
Cholangiographic features of PSC include predominantly intrahepatic ductal disease with short multiple strictures associated with multifocal mild ductal dilations. Cholangiography demonstrates a pruned-tree appearance with filling of the central ducts and diffuse obstruction of the peripheral smaller radicles. More advanced disease is associated with long strictures.
Bile duct dilations may result from the inflammatory process or distal obstruction. Multifocal strictures have a predilection for bifurcations. Skip lesions may be observed in which the duct is of normal caliber.
The above features provide a beaded appearance to the ducts. Coarse nodularity with mural irregularities may produce a cobblestone appearance. Ductal diverticula or pseudodiverticula observed as small saccular outpouchings are pathognomonic findings for PSC.
The common bile duct (CBD) is almost always involved.
The cystic duct also shows strictures, mural nodularity, and dilations with diverticula formation in 18% of patients. Gallbladder irregularity is uncommon. Pancreatic duct strictures and irregularities are observed in 8% of patients. 
Intrahepatic pigment calculi, which are easily crushable, are found in 8% of patients and may cause mechanical obstruction. Rarely, these calculi may obstruct the CBD; however, bile duct dilatation may not occur in the presence of cholangiocarcinoma. 
Appearances of the terminal bile ducts vary, particularly on ERCP, and overinterpretation is common. To tackle this problem, numerous views are obtained at various stages of contrast filling, which may help resolve equivocal changes. Radiographic distinction between a cholangiocarcinoma and sclerosing cholangitis occasionally may be impossible, because the diagnostic specificity of intrahepatic bile duct changes remains controversial.
Ascending cholangitis, AIDS-related cholangiopathy, cholangiocarcinoma, chemotherapy-induced cholangitis, eosinophilic cholangitis, recurrent pyogenic cholangitis, cholangitis secondary to parasites, and primary biliary cirrhosis can produce similar radiographic appearances.
Intrahepatic bile duct changes demonstrated on CT scans reflect cholangiography features with pruning and beading of the ducts. Pruning on CT scans is defined as the presence on a single CT slice of a 4-cm or longer segment of dilated duct (excluding the main right and left ducts) that lacks the expected side branching. Beading is defined as at least 3 closely alternating regions of change in caliber in an intrahepatic duct on a single CT slice.
Skip dilatations, defined as isolated dilated peripheral bile ducts with no visible connection to the other dilated ducts on contiguous images, are strongly suggestive of PSC.
CT appearances of extrahepatic bile duct involvement by PSC include focal or diffuse eccentric or concentric involvement and wall thickening (>2 mm and < 5 mm), bile duct dilatation, relative lack of dilatation proximal to an apparent bile duct stricture, and enhancing intraluminal intramural nodules (>1 cm in diameter) seen on thin-section high-resolution images.
Contrast enhancement of the bile duct is a nonspecific finding that can be observed in normal and abnormal bile ducts.
Lymph nodes are usually homogeneous and isodense with the pancreas.
Intrahepatic bile duct changes on CT scans reflect cholangiographic features with pruning and beading of the ducts. Skip dilatations, defined as isolated dilatation of the intrahepatic bile ducts, are strongly suggestive of PSC; however, ductal delineation and demonstration of strictures can be difficult in the early stages using US or CT scans. CT has a complementary role to that of cholangiography; moreover, do not use CT as a screening examination.
Beading, pruning, irregularity, and asymmetry of the intrahepatic bile ducts as demonstrated on CT scans are not specific for PSC. Similar CT changes may be found in other forms of cholangitis and cholangiocarcinoma.
The AASLD and the EASL have both recommended magnetic resonance cholangiopancreatography (MRCP) as the first-line modality for imaging bile duct abnormalities in PSC. The advantages of MRCP are that it is noninvasive and does not require contrast media or ionizing radiation.  Characteristic findings on MRCP include multiple segmental strictures with slightly dilated ducts on both intrahepatic and extrahepatic ducts.  However, MRCP may have limited accuracy in early PSC. Therefore, ERCP remains the mainstay for accurate diagnosis of ERCP through analysis of the hepatobiliary tree because of its higher sensitivity. 
As the disease progresses, a pruned-tree appearance may become visible as small peripheral ducts become obliterated. 
Use of T1-weighted, fat-suppressed, spin-echo pulse sequences, with or without intravenous gadolinium, facilitates visualization of the bile duct wall. Peripheral, wedge-shaped areas of high T2-weighted signal intensity in the liver parenchyma and dilatation of the bile ducts are characteristic MRI features of PSC observed in approximately 72% of patients.
Associated features include periportal edema (40%), lobar atrophy (8-28%), and portal hypertension (35%).
Abnormal hyperintensity of the liver parenchyma on T1-weighted images may be observed in 23% of patients. Increased enhancement of the liver parenchyma on dynamic arterial-phase gradient-echo images, predominantly in the peripheral areas, may be observed in 56% of patients. Periportal inflammation may be demonstrated on MRI images as a region of low signal intensity on T1-weighted images and as intermediate signal between liver and bile on T2-weighted images.
On gadolinium-enhanced images, enhancement of inflammatory periportal tissue permits distinction from nonenhancing periportal edema.
Characteristic changes on MRI have been recognized within the pancreas, suggestive of PSC. Increased signal on T2-weighted images, decreased signal on T1-weighted images, enlargement of the pancreas, and decreased contrast enhancement are suggestive of pancreatic disease associated with PSC.
The addition of diffusion-weighted MRI to standard MRCP protocols is valuable in the diagnosis of PSC and the evaluation of disease severity. Moreover, diffusion-weighted imaging could be used in continuation with standard MRI sequences for the evaluation of liver fibrosis stage and distribution. 
Gadolinium-based contrast agents have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see Nephrogenic Systemic Fibrosis. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see Medscape.
The number of patients with PSC who have been studied using MRI has been small; thus, the reliability of the changes described above is uncertain. MRCP may be used, but the extent of intrahepatic disease may be estimated incorrectly because ductal distention cannot be achieved using MRCP.
MRI features of PSC are not specific and may occur with cholangiocarcinoma and other forms of cholangitis.
Ultrasonographically, biliary abnormalities are not usually visible, unless biliary dilatation is associated. Intrahepatic saccular dilations occasionally may be visualized, and in long-standing disease, echogenic intraductal structures, representing sludge or calculi, are visible on US images. Bile duct wall thickening and small intraluminal protrusions also have been reported in patients with PSC. In end-stage disease, US signs of portal hypertension may be demonstrated.
Secondary biliary cirrhosis occurs as a part of the disease complex of PSC. Most patients with secondary biliary cirrhosis have no ultrasonographic abnormalities, but occasionally, irregular segmental duct dilatation can be observed.
Patients with advanced disease may show an increase in periportal echogenicity.
Cirrhotic changes, such as nodularity-increased liver attenuation and splenomegaly, also may be apparent.
US appearances of PSC are nonspecific; seldom can a confident diagnosis of PSC be made using US alone. The primary role of US is in the diagnosis of other causes of obstructive jaundice.
The differential diagnosis includes cholangiocarcinoma and other causes of ascending cholangitis and primary biliary cirrhosis. In addition to PSC, bile duct wall thickening is associated with hepatic clonorchiasis, recurrent pyogenic cholangitis (Oriental cholangiohepatitis), biliary ascariasis, peribiliary cysts, and AIDS-related cholangiopathy.
Radionuclide scanning using technetium-99m (99mTc) iminodiacetic acid compounds shows multiple focal areas of persistent activity distributed in the liver parenchyma. The clearance rate of the isotope through the liver is markedly prolonged, with gallbladder visualization achieved in 70% of patients. [23, 31] The specificity of 99mTc iminodiacetic acid scanning is low, but it is a valuable technique to use for quantifying biliary kinetics. (See the image below.)
Prolonged isotope transit time may occur in other causes of hepatic dysfunction; similarly, nonvisualization of the gallbladder may occur with cystic duct obstruction and chronic gallbladder disease.
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Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK
Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England
Disclosure: Nothing to disclose.
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR Chief Medical Officer, Silk Road Medical
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR is a member of the following medical societies: British Medical Association, Cardiovascular and Interventional Radiological Society of Europe, British Society of Interventional Radiology, International Society for Vascular Surgery, Royal College of Physicians, Royal College of Radiologists, British Society of Endovascular Therapy, Scottish Radiological Society, Vascular Society of Great Britain and Ireland
Disclosure: Received salary from Silk Road Medical for employment.
Aali J Sheen, MD, MBChB, FRCS Consulting Hepatobiliary Surgeon, HepatoBiliary Unit, Manchester Royal Infirmary, UK
Aali J Sheen, MD, MBChB, FRCS is a member of the following medical societies: British Medical Association, International Hepato-Pancreato-Biliary Association, Royal College of Surgeons of England
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
Arnold C Friedman, MD, FACR Professor, Department of Radiology, University of Florida Health Science Center; Chief, Department of Radiology, Shands-Jacksonville Hospital
Arnold C Friedman, MD, FACR is a member of the following medical societies: American College of Radiology, American Institute of Ultrasound in Medicine, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America
Disclosure: Nothing to disclose.
John Karani, MBBS, FRCR Clinical Director of Radiology and Consultant Radiologist, Department of Radiology, King’s College Hospital, UK
John Karani, MBBS, FRCR is a member of the following medical societies: British Institute of Radiology, Radiological Society of North America, Royal College of Radiologists, Cardiovascular and Interventional Radiological Society of Europe, European Society of Radiology, European Society of Gastrointestinal and Abdominal Radiology, British Society of Interventional Radiology
Disclosure: Nothing to disclose.
Eric P Weinberg, MD Associate Professor, Department of Radiology, University of Rochester Medical Center, Strong Memorial Hospital
Disclosure: Nothing to disclose.
Primary Sclerosing Cholangitis Imaging
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