Imaging of Pancreatitis

Abstract

Imaging of pancreatitis is very complicated. Correct detection of the various forms of pancreatitis is essential for adequate early therapy. In acute pancreatitis, imaging is useful for diagnosis, but above all for the research of causes and any complications. In autoimmune forms, imaging raises clinical suspicion and guides the response to therapy and the search for associated pathologies. In chronic pancreatitis, imaging is essential for grading, differential diagnosis with neoplastic diseases and follow-up. The classical CT and MRI methods play a fundamental role in this sense, being increasingly supported by modern special techniques such as S-MRCP and T1-mapping. Finally, interventional radiology today represents one of the main minimally invasive methods for the diagnosis and treatment of complications.

1. Introduction

Imaging of pancreatitis is complex and requires in-depth knowledge of both radiological techniques and pathophysiology, pathology and clinical manifestation of these diseases. In fact, pancreatitis has very different forms and manifestations, which require completely different treatments, therefore imaging, especially CT and MRI, are fundamental for the early classification and the consequent therapy. Furthermore, many forms of pancreatitis enter into differential diagnoses with other non-inflammatory conditions of the pancreas, for which a correct diagnosis as early as possible is essential. In this chapter, we will analyze the imaging aspects of acute pancreatitis, chronic pancreatitis and rarer forms such as autoimmune and paraduodenal.

2. Acute pancreatitis

Acute pancreatitis (AP) is an acute inflammatory condition with a range of severity and various local and systemic complications. The main etiologies are the presence of gallstones or alcohol abuse (75–80%); other causes are pancreatic tumors, traumatic or iatrogenic damage and drugs (thiazide diuretics, steroids, azathioprine). In 10–15% of patients, the cause is not identified [1].

The 2012 Revised Atlanta Criteria is an update of the 1992 original classification of AP and is aimed to clarify and improve the terminology of severity grading and local complications. AP is now divided into two distinct subtypes based on the presence or the absence of parenchymal necrosis: necrotizing pancreatitis (NP) and interstitial edematous pancreatitis (IEP). Patients can develop four distinct collection subtypes that are identified based on the presence of pancreatic necrosis and the time elapsed since the pancreatitis onset (with 4 weeks as a threshold). Acute peripancreatic fluid collections (APFCs; <4 weeks) and pseudocysts (PSCs: >4 weeks) occur in IEP and contain fluid only. Acute necrotic collections (ANCs; <4 weeks) and walled-off necrosis (WONs: >4 weeks) occur only in NP and contain fluid with necrotic debris. APFCs and ANCs are acute complications and they may either resolve or persist, developing a mature wall to become delayed complications such as PSCs or WONs, respectively. In addition, any collection subtypes may become infected and may lead to other local or systemic complications [2, 3].

The pancreatitis severity scale has also been updated to improve the stratification and the management of patients; to the original categories of mild and severe AP, based on the presence of organ failure, a third moderately severe AP category has been added for patients with local complications, substantial morbidity and low mortality. A variety of imaging-based scoring systems can be applied to predict severity although they do not account for risk factors like obesity. The computed tomography severity index (CTSI) is the most commonly used and recommended scoring system, it combines the Balthazar grade with the extent of the pancreatic necrosis on a 10-point severity scale as shown in Table 1.

Pancreatic features	Balthazar grade	CTSI 0–3 = mild 4–6 = moderate 7–10 = severe
Normal gland	A	0
Local or diffuse swelling	B	1
Peripancreatic fat stranding	C	2
Single acute fluid collection	D	3
≥ 2 acute fluid collections	E	4
No necrosis		0
<30% of necrosis		2
30–50% of necrosis		4
>50% of necrosis		6

Table 1.

Imaging-based scoring systems.

Radiological examinations offer various imaging modalities which play specific roles in the different phases of acute pancreatitis. In the early phase, during the first week after onset, imaging aims to establish the diagnosis, determine the etiology and stage the severity; in the late phase, imaging is needed to establish and monitor complications and to guide interventional procedures.

2.1 Imaging in the early phase

The onset of pancreatitis is considered to coincide with the first day of pain; in the first week after onset, the imaging findings correlate poorly with the clinical severity, but they may be useful in assessing the cause of acute pancreatitis [1].

The 2012 Revised Atlanta Classification requires two or more of the following criteria to make a diagnosis of AP: a) abdominal pain suggestive of pancreatitis, b) serum amylase or lipase level greater than three times the upper normal value, c) characteristic imaging findings.

Thus, imaging in the initial diagnosis of AP is requested only if the other criteria are not conclusive for the diagnosis but is still necessary in the assessment of the cause of AP.

Ultrasound (US) is the primary imaging technique for the assessment of the biliary tract and should be performed in every patient to rule out gallstones; the examination can also show pancreatic swelling, dilatation of the pancreatic duct or secondary findings like gallbladder or choledochal wall thickening, pericholecystic fluid or fat stranding. The major disadvantage of US is the limited visibility of the pancreatic region because of the presence of overlying bowel gas; moreover, US is poorly accurate in delineating extra pancreatic inflammatory spread and in detecting intrapancreatic necrosis [4, 5].

The American College of Gastroenterology and the American College of Radiology appropriateness criteria recommend performing contrast-enhanced computed tomography or magnetic resonance imaging only in patients with an unclear diagnosis or who do not improve within 48–72 hours of admission [1]. In fact, early CT is indicated if a complication is suspected, even if parenchymal necrosis may be misdiagnosed due to edema and vasoconstriction. The use of a contrast medium is essential for detecting parenchymal necrosis and vascular complications; the standard examination includes an unenhanced phase, a pancreatic phase (delay of 40–50 s) and a portal venous phase (delay of 60–70 s). A monophasic CT protocol is usually sufficient for the diagnosis and the progression assessment, while dual-phase studies (arterial and portal venous) are recommended in case of suspicion of hemorrhage, mesenteric ischemia or arterial pseudoaneurysm or pancreatic mass [3, 5, 6]. In IEP imaging shows a focal or diffuse pancreatic enlargement and an entire parenchymal enhancement with no unenhanced areas (Figure 1), although enhancement may be less avid than that of the normal pancreas due to the interstitial edema.

Figure 1.

F, 64 yo, affected by an acute interstitial edematous pancreatitis; At CT a homogeneous decreased enhancement of the entire pancreas is appreciable with no evidence of non-enhancing areas (a); at the level of the tail, a peripancreatic collection is noticeable (b).

Necrotizing pancreatitis (NP) account for 5–10% of all AP and in the early phase, pancreas can appear edematous and hypoenhancing like in IEP, then non-enhancing areas appear as a sign of pancreatic necrosis, which evolves over time (Figure 2). There are three subtypes of NP based on the distribution of the necrotic areas: pancreatic NP (5%) without peripancreatic collections, peripancreatic NP (20%) showing peripancreatic necrosis with collections of fluid and components, combined NP (75%) characterized by non-enhancing pancreatic areas and heterogeneous peripancreatic collections [1]. The different subtypes of NP can be observed in the same patient at different times (Figure 2).

Figure 2.

F, 78 yo, affected by a biliary NP. The patient underwent a CT follow-up that showed a progressive lack of enhancement in the body-tail of the pancreas with large necrotic collections.

CT shows the extension of the inflammatory process, but it has a limited capability of differentiating homogeneous fluid collection from debris within collections; moreover, CT has a limited capability of differentiating small necrotic areas from local effusions or focal adipose depositions in elderly people [7].

MRI is an alternative imaging technique especially indicated in case of renal failure, young patients and pregnant women; it is superior to CT in the characterization of pancreatic collections identifying the presence of debris or necrotic material, although its longer scanning time makes its use difficult in uncooperative patients. Moreover, it is useful in the diagnosis of AP when other criteria are inconclusive and US is still uncertain, thanks to its superior sensitivity to pancreatic edema (Figure 3). MRI, especially with cholangiopancreatography (MRCP) shows high sensitivity and specificity for choledocholithiasis or congenital anomalies which can explain the AP.

Figure 3.

F, 74 yo with the diagnosis of IEP. Patient with 8x increase of lipase and amylase, pain, gallbladder calculi (a) but a normal-sized pancreas at US (b). At CT (c) no significant alterations of the pancreatic parenchyma are appreciable, but a slight peripancreatic fluid collection in the tail. At MRI, a slight peripancreatic fluid collection is appreciable with different sequences: T2 (d), DWI and ADC map (f, g, h), while pancreatic parenchyma does not show significant alterations at T1WI (e). With DWI, slight parenchymal edema is appreciable in the tail; gallbladder calculi (i).

MRI features of IEP include a slight parenchymal hypointensity on T1WI and hyperintensity on T2WI. There may be acute peripancreatic fluid collections showing patchy-like hyperintensity on T2WI in the peripancreatic region, pararenal spaces and lesser omental bursa. Diffusion-weighted imaging (DWI) technique allows a better appreciation of slight pancreatic edema (Figure 3).

After contrast agent administration, the pancreas shows homogeneous enhancement. In NP the necrotic areas are hypointense on T1WI, hyperintense on T2WI and have no enhancement after contrast medium. Collections around the pancreas show mixed intensity on T1WI and T2WI, but no enhancement [3, 8].

2.2 Imaging in the late phase: follow up and complications

Imaging is most useful if performed 5–7 days after the onset of AP, when pancreatic necrosis, collections and local complications are distinguishable. The Revised Atlanta Criteria distinguishes the collections that contain purely fluid in IEP from the collections that contain also necrotic debris in NP. The distinctions for classifying collections are the time course (≤ 4 or > 4 weeks from the onset of pain) and the presence of necrosis at imaging [1].

APFCs are diagnosed during the first four weeks in patients with IEP; they are peripancreatic homogeneous fluid collections without a wall and tend to conform to the retroperitoneal spaces (Figure 4). When a similar collection is seen within the pancreatic parenchyma, it is by definition an ANC and the diagnosis is NP. At MRI APFCs are homogeneously hypointense on T1WI and hyperintense on T2WI [1, 8]. Most APFCs resolve spontaneously, the drainage should not be performed because of the risk of infecting a sterile collection. Pseudocyst develops in fewer than 10% of IEP when an APFC does not resolve within four weeks and becomes more organized with a wall containing only fluid (Figure 4); it is called pseudocyst because lacks a true epithelial tissue. At MRI pseudocysts are uniformly hyperintense on T2WI, with no solid components or debris, and have a thin smooth wall; they may have a connection to the ductal system.

Figure 4.

M, 49 yo. CT images show acute peripancreatic fluid collections (a) within four weeks from the onset of interstitial edematous pancreatitis and the development of a pseudocyst four weeks later (b).

ANCs are poorly organized necrotic collections that develop in NP within the first four weeks of symptoms; they are usually found in the lesser sac, in the pararenal spaces or extended into the pancreatic parenchyma with a lobulated appearance and containing solid or fat debris (Figure 5). Any collection associated with an NP should be termed an ANC, even if it is homogeneous without debris. At MRI, ANCs show mixed signals on T1WI and T2WI, with flocculent unenhanced low signal necrotic areas [1, 3, 8]. WON is an ANC that after four weeks develops a thick enhancing wall containing fluid and debris of necrotic fat or pancreatic tissue (Figure 5); it may be confined to the pancreatic parenchyma or be in the peripancreatic space. At MRI, a WON shows a well-defined T2-hypointense, gadolinium-enhancing wall and contains non-liquid substances floating [1, 3, 8]. Differentiating a pseudocyst from a WON is important because WON does not respond to endoscopic cyst gastrostomy, but requires surgical debridement [3]. A pseudocyst is peripancreatic with homogeneous fluid, while WON contains necrotic material and can involve both pancreatic and peripancreatic tissue. MRI outperforms CT in the assessment of fluid and necrotic debris in the collections for planning interventions [7].

Figure 5.

F, 83 yo. CT follow-up of a patient with necrotizing pancreatitis showing the progression over time from an acute necrotic collection (a) to walled-off necrosis (b); the late infection of the collection (c) required surgical intervention.

Any collection can be sterile or infected, the only imaging finding of infection is the presence of gas appearing as multiple small bubbles scattered throughout the collection (Figure 5). According to some authors, MRI with DWI shows high sensitivity (100%) and specificity (91%) in detecting infection of collections, even when CT is doubtful due to the lack of bubble gas. On the ADC map the collection shows a target appearance, bright at the center and black at the periphery of the collection, with a similar appearance to a hepatic abscess [9].

The imaging-guided aspiration of fluid collections or the fine-needle aspiration of necrotic tissue can help to diagnose the infection before invasive surgery but can cause iatrogenic infection. Percutaneous drainage is preferred to the fine-needle aspiration because the culture of the fluid can be easily performed; the fine-needle aspiration remains helpful when clinical and imaging findings are confusing [1, 3].

Pancreatic collections may have an extrapancreatic spread resulting in intrasplenic collection or abscess, splenic infarction or intrasplenic hemorrhage; similar complications may occur in the liver. In these cases, the pancreatic enzymes may extend into the mesenteries and can cause bacterial translocation, bowel ischemia and perforation. Moreover, necrotic collections can erode the bowel wall (especially the wall of the colon and duodenum in 4% of NP) and create a pancreatic-enteric fistula that also manifests gas bubbles in infected collections. Renal involvement is usually due to the inflammatory spread to pararenal spaces, the left space is the one commonly involved by vascular abnormalities [10].

Other main complications are due to the involvement of vascular structures and can lead to developing portal system thrombosis or arterial pseudoaneurysms. Splenic vein thrombosis is the most common complication and may result in gastric varices or splenomegaly [3]. Arterial pseudoaneurysms can lead to life-threatening hemorrhages when the extravasated pancreatic enzymes erode the walls of splenic, pancreaticoduodenal or gastroduodenal arteries [3]. In these cases, the interventional radiology approach is recommended to perform fast and selective vessel embolization with coils or glue (Figure 6).

Figure 6.

F, 56 yo with upper gastrointestinal bleeding a month after acute pancreatitis onset; CT detected a pseudoaneurysm of the superior pancreaticoduodenal artery due to walled-off necrosis (a, b). The patient underwent an emergent percutaneous angiography that confirmed the extravasation of the contrast medium (c) and selective embolization of the culprit branches (d).

3. Recurrent acute pancreatitis

Recurrent acute pancreatitis (RAP) is a common clinical problem, among the first causes of emergency and expense for gastroenterological pathologies in US [11, 12]. Common complications such as the evolution to episodes of acute pancreatitis, the onset of diabetes or the progression to chronic pancreatitis represent an eventuality with a serious impact on the patient’s quality of life and on healthcare costs [13]. About one-third of cases of acute pancreatitis have a recurrence, resulting in the onset of chronic pancreatitis over time [14]. In these cases, it is important since the first episode of pancreatitis to study its causes in order to be able to prevent the onset of new ones, thus avoiding progression to chronic forms. In this sense radiology plays an important role, allowing to identify the causes early and treat them promptly, improving the patient’s outcome. In fact, the idiopathic forms of acute pancreatitis, those without an apparent underlying cause that can be treated, have a significantly worse outcome [15].

Clinically it is defined as RAP when two or more episodes of pancreatitis are documented three months apart [14]. The underlying causes of RAP are primarily biliary and alcoholic. There are also rarer causes, such as hypertriglyceridemia, about 5%, autoimmune pancreatitis (AIP) and genetic causes. For this reason, it is always recommended to measure blood triglycerides, search for possible autoimmune etiologies (especially type II AIP), and search for mutations affecting at least four genes, especially in young patients with early onset of acute pancreatitis, in which a genetic mutation exists very frequently [11, 16].

However, radiology is crucial in identifying only some of these causes of recurrent pancreatic inflammation, in particular those of biliary origin, those related to an anomaly of the pancreatic ductal system, a sphincter of Oddi dysfunction (SOD) or other causes of intrapancreatic obstruction.

Although CT and MRI are first-level methods for studying the pancreatic and biliary ductal system, currently the gold standard to identify small calculi or even small tumors that hinder the outflow of pancreatic juice is endoscopic ultrasonography (EUS) [17]. However, this is a highly operator-dependent method, which requires high expertise of the physician and which is not available in all centers. For this reason, CT and MRI are more commonly used. CT is useful for detecting ductal obstructions due to calcific stones. MRI with cholangiopancreatography (MRCP), on the other hand, allows evaluation of the anatomy and possible anomalies of the pancreatic duct and its branches. Both methods allow us to study the pancreatic parenchyma, in order to identify those causes of RAP that originate from parenchymal disease, such as AIP, which will be discussed later. Radiology also has the role of identifying and characterizing any intraductal papillary neoplasms (IPMN), which can be the cause of RAP. Both main duct and branch ducts IPMNs produce mucus, which is viscous and can temporarily obstruct the outflow into the main pancreatic duct, causing small painful colic that can also lead to real episodes of pancreatitis that recur over time. In this case, MRI is essential to characterize pancreatic cystic lesions and above all to clarify their communication with the ductal system in IPMNs (Figure 7). Other causes of the obstacle to the outflow of pancreatic juice that can be effectively studied with radiology are congenital variants of pancreatic ducts. The main anatomical anomaly of the ducts is the pancreas divisum (Figure 8), in which the pancreatic duct remains divided into its two embryonic components: the ventral duct and the dorsal duct. However, only about 5% of the population has this anatomical variant and among them, only 5% will develop symptoms of RAP [18]. Pancreas divisum is classically classified into three types: type 1 is when there is an incomplete fusion between the ventral and dorsal ducts (more common), type 2 is when there is the total dominance of the dorsal duct with complete absence of the Wirsung duct, while type 3 is when there is a thin communication between the two ducts (incomplete divisum) [19].

Figure 7.

Male, 66 yo with RAP (3 episodes). Dilatation of the main pancreatic duct (arrows) is appreciable in the tail of the pancreas, both at T2w (a) and MRCP (b), compatible with MD-IPMN.

Figure 8.

M, 41 yo. History of recurrent epigastric pain. At MRCP a pancreas divisum is visible with a small ectasia at the level of the minor papilla (santorinicele).

MRCP is also important for detecting the presence of a santorinicele with high sensitivity, which can be one of the causes of pancreatic outflow impairment (Figure 8).

S-MRCP is a morpho-functional method that requires the administration of secretin to the patient and the serial acquisition of MRCP images to evaluate the various phases of pancreatic secretion in the duodenum [20]. In a healthy pancreas, 1 minute after administration, a filling with minimal dilation of the main pancreatic duct and all the side branches is expected, starting to glimpse a duodenal filling. After 5 minutes the ductal system is completely relaxed and the duodenum filled with liquid. In case of impaired functional alterations, such as SOD, which is not detectable with morphological imaging, this physiological flow in the duodenum is not observed and the ductal system remains dilated for a longer time, without emptying regularly (Figure 9).

Figure 9.

M, 42 yo. Recurrent abdominal pain with amylase elevation. S-MRCP during (a) and 5 minutes after (b) administration of secretin. The main duct persists dilatated even after 5 minutes, the diagnosis is compatible with SOD. The physiological duodenal filling is delayed but partially conserved.

S-MRCP is useful for identifying cases of santorinicele, as well as for evaluating the effects of sphincterotomy [21]. Finally, it is useful for highlighting any anatomical anomalies of the ducts not clearly visible to the common MRCP which can lead to obstructive disease, as previously described.

4. Paraduodenal pancreatitis

Paraduodenal pancreatitis (PDP) is a form of chronic pancreatitis which involves the duodenal wall near the papilla minor and the nearby pancreatic parenchyma or the space interposed between them, named pancreatic groove [22]. The disease is strictly related to ethanol abuse, affecting mainly 40–50 years old males [23]. Clinical manifestations resemble those of chronic pancreatitis, with recurrent pain in the upper abdomen exacerbated by eating, nausea and weight loss. Rarer is obstructive jaundice, which is more typical of pancreatic cancer, but tumor markers are negative [24]. Different pathological entities are grouped in PDP diagnosis. Groove pancreatitis is the most common; it is characterized by the formation of scar tissue between the duodenal wall and the neighbor pancreatic parenchyma, caused by an anatomical or functional obstruction of minor papilla outflow [25, 26]. Even the presence of ectopic pancreatic tissue can cause paraduodenal pancreatitis, leading to paraduodenal wall cysts formation. These usually involve the descending part of the duodenum and are mostly located in the submucosa [24].

In paraduodenal pancreatitis, CT usually shows a hypoattenuating solid mass in the pancreatic groove with duodenal wall thickening often visible, sometimes associated with cystic lesions. The presence of duodenal wall thickening and cystic changes may help to differentiate PDP from pancreatic cancer, where these findings are rare. Duodenal stenosis with gastric outlet obstruction is an uncommon finding but it is more frequent than in pancreatic cancer [27, 28].

MRCP is the gold standard for the study of paraduodenal pancreatic lesions. In solid forms, MRI shows a hypointense lesion near the duodenal wall at T1-weighted imaging, with a variable signal in T2-weighting (Figure 10) [29].

Figure 10.

M, 45 yo. Alcohol abuse. Recurrent epigastric pain. Paraduodenal pancreatitis. A small cystic lesion in the groove area is appreciated (a), embedded in a hypointense soft tissue mass (b), hypovascular (c, d), with delayed enhancement (e). At MRCP the cystic lesion is well appreciated (arrow, f).

The enhancement of these lesions both at CT and MRI is related to their high fibrous content, with a slow progressive enhancement, not visible in the arterial phase, where the lesion appears hypovascular, but with a later homogenous enhancement, thus allowing to distinguish PDP from PDAC, which usually tends to remain hypovascular even in the later acquisition phases (Figure 10) [24].

MRI is also fundamental for studying cystic forms of PDP, first of all highlighting their fluid content, and then studying their relationship with the duodenal wall, with the ductal system and with the healthy pancreatic parenchyma or with fibrotic changes (Figure 10). MRCP sequences are essential for evaluating the relationship between the duodenum and intrapancreatic choledochus; in particular, while in pancreatic cancer the choledochus is more frequently irregularly stenotic and infiltrated by the neoplasm, with marked upstream dilation of the biliary tree, in PDP it is more frequently smoothly narrowed and displaced, and therefore the MRCP shows an increase in the physiological space between the choledochus and the lumen of the duodenum (Figure 10) [30]. In the same way, the gastroduodenal artery can be displaced in PDP instead of being infiltrated in pancreatic cancer (Figure 10).

Although imaging is important for the study of PDP, both for solid and cystic forms, it is not always possible to make a differential diagnosis, in particular with PDAC, cholangiocarcinoma or cancer of the duodenal wall which has a worse prognosis and require different treatments [29, 31]. Laboratory tests and tumor markers can help to sort out the diagnosis, but it is often necessary to combine EUS investigations with tissue sampling to rule out the presence of cancer.

5. Autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is an uncommon form of pancreatitis characterized by frequent the presentation of focal or diffuse pancreatic enlargement with (when the lesion affects the pancreatic head) or without obstructive jaundice, caused by a histological lymphoplasmacytic infiltrate and fibrosis and characterized by a dramatic response to steroids [32]. Two forms of AIP are classified based on clinical and histopathological findings. AIP type 1 is characterized by lymphoplasmacytic sclerosing pancreatitis without granulocyte epithelial lesions, with the presence of dense infiltrate of IgG4 positive plasma cells, being an expression of an IgG4-related systemic disease often characterized by extrapancreatic lesions (i.e., sclerosing cholangitis, sclerosing sialadenitis, and retroperitoneal fibrosis). AIP type 2, on the other hand, refers to idiopathic duct-centric pancreatitis with granulocyte epithelial lesions; this condition does not appear to be associated with IgG4-related systemic disease but it can be associated with an inflammatory bowel disease. In this latter condition, pancreatic enlargement may not be visible but stenosis of the Wirsung duct is characteristic.

The role of radiology in AIP is fundamental, as it can characterize it and distinguish it from PDAC in the case of focal AIP, allowing correct management of this disease.

MRI with MRCP allows both to evaluate the pancreatic parenchyma, its enhancement, and the morphology of the ductal system [33, 34]. Furthermore, DWI imaging, evaluating the microscopic movement of water molecules, can show a restricted diffusion due to the presence of cellular infiltrate that limits the water movement. The imaging findings must be understood considering that histopathology of AIP includes a periductal infiltrate which leads to an increase in the size of the pancreatic gland and at the same time to a compression of the ductal system; another important aspect that characterizes AIP is the presence of obliterating vasculitis [32, 35, 36]. This is important because these two factors, hypovascularization and ductal stenosis, can radiologically mimic pancreatic cancer. Therefore, AIP exhibits imaging features that may be typical or atypical.

Typical AIP is characterized by diffuse (“sausage-like”) enlargement of the gland with a loss of physiological lobulation due to an increase in tissue pressure with delayed enhancement, sometimes associated with rim-like enhancement. In AIP at MRCP the main pancreatic duct presents a long reduction of the caliber (more than 1/3 of the length of the main pancreatic duct) or multiple strictures without significant upstream dilatation (Figure 11), differently from pancreatic cancer where the stenosis is focal with marked upstream dilatation.

Figure 11.

M, 55 yo. Autoimmune pancreatitis, diffuse form. A diffuse enlargement of the pancreas is appreciable (a), showing restricted diffusion with high signal intensity on DWI (b), hypovascular in the arterial phase (c) but showing late homogeneous enhancement (d). At MRCP (e), the Wirsung duct is not appreciable due to the compression from the enlarged pancreas but returns to normal after steroid therapy (f).

However, some AIP presents with an atypical appearance, showing low-density focal mass at CT, pancreatic duct upstream dilatation, or distal atrophy of the parenchyma. These atypical imaging findings in patients with obstructive jaundice are highly suggestive of pancreatic cancer and should be managed as pancreatic cancer unless there is strong evidence for AIP, and a precise workup for cancer is negative [32]. However, the presence of segmental or focal enlargement of the pancreas with delayed enhancement, highly restricted diffusion and focal narrowing of the main pancreatic duct without marked upstream dilatation (<5 mm), are imaging signs that may aid in the differential diagnosis between atypical AIP and pancreatic cancer (Figure 12). If the stenosis is focal and single, the possibility of pancreatic cancer is high, but if the stenosis is two or more, it could be a case of atypical AIP [37, 38].

Figure 12.

M, 69 yo. Jaundice. Autoimmune pancreatitis, focal form. A focal enlargement of the head of the pancreas is appreciable (a), showing restricted diffusion with high signal intensity on DWI (b), hypovascular in the arterial phase (c) but showing late homogeneous enhancement (d). At MRCP (e), marked stenosis both of the Wirsung duct and choledochus is appreciable, simulating a “double duct sign”, typical of PDAC. After steroid therapy (f) both Wirsung duct and choledochus return to normal.

6. Chronic pancreatitis

Chronic pancreatitis (CP) is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathologic response to parenchymal injury or stress.

CP is most commonly caused by toxins such as alcohol or tobacco, genetic polymorphisms and recurrent attacks of acute pancreatitis.

Early diagnosis of CP is fundamental because early CP is the stage in which target therapy is likely to be most effective.

According to American College of Gastroenterology 2020 guidelines, in patients with clinical symptoms of a pancreatic inflammatory disorder and/or in patients with a suggestive gene–environment risk assessment, cross-sectional imaging, in particular, CT or MRI with MRCP, should be the first-line tests for the diagnosis of CP, because they are valid, reproducible, widely available and non-invasive. Because of its invasiveness and minor reproducibility and availability, EUS should be used after cross-sectional imaging when the diagnosis is still in doubt, or if there is a concern about “minimal changes” that cannot be visualized on cross-sectional imaging. If CT, MRI with MRCP and EUS do not confirm the diagnosis of CP and the suspicion is still high, S-MRCP is suggested because it allows better visualization of the main pancreatic duct and side branches and allows to obtain a semiquantitative measurement of duodenal filling [39].

In CP impaired outflow of pancreatic juice induces inflammation and fibrotic replacement of pancreatic parenchyma; fibrosis is responsible for reduced ductal compliance and ductal anomalies (such as side branches ectasia in early-stage and dilatations, strictures and irregularities of the main pancreatic duct in advances stages), while inflammation causes intraductal and parenchymal calcifications.

At imaging, in early chronic pancreatitis morphology and dimensions of the pancreas are normal, but impairment of pancreatic juice outflow drives mild fibrosis; in overt CP, the main pancreatic duct is dilatated and distorted, pancreatic parenchyma is thinned and may contain cysts, and intraductal and parenchymal calcifications are present.

The role of the radiologist in the early stage is to make a diagnosis of CP and look for its causes (so that they can be removed if possible), while in the advanced phase the role of the radiologist is to confirm the diagnosis, look for its causes, identify complications, monitor the disease and early detect pancreatic adenocarcinoma (PDAC) for which these patients are at increased risk [40]. The most valid radiological techniques to diagnose and monitor CP are CT, MRI with MRCP and S-MRCP.

CT and MRI have similar sensitivity and specificity in diagnosing CP, respectively 75% and 91% for CT and 78% and 98% for MRI [41]. CT is cheaper, easily available, allows rapid visualization and characterization of calcifications and is much faster, thus can be used also in uncooperative patients; on the other hand, MRI allows better identification of early parenchymal alteration and subtle ductal changes so it is the best technique to diagnose early CP; moreover, it is the best technique to monitor disease progression, to early detect pancreatic ductal adenocarcinoma (for which patients with CP are at increased risk) and is useful in differentiating focal CP from PDAC and CP from IPMN. In any case, the two techniques may be considered complementary.

6.1 MRI imaging

MRI is the best technique to early diagnose and follow up CP, thanks to its intrinsic high contrast resolution because it provides optimal visualization of the pancreatic ductal system.

MRCP are key sequences for evaluating the pancreatic ductal system and are acquired using 2D and/or 3D heavily T2 weighted sequences in which structures containing static fluid appear markedly hyperintense while surrounding solid structures display very low signal and appear markedly hypointense (Figures 8–12).

The best sequence to evaluate pancreatic borders and pancreatic parenchyma is GRE T1 fat-sat (either with Dixon technique), because of the intrinsic signal differences between the high signal intensity of the pancreatic parenchyma and the suppressed signal of the peri-pancreatic fat. With this sequence, the healthy pancreas, whose cells are rich in proteins, appears homogeneously hyperintense while the fibrotic replacement of acinar cells leads to a progressive decrease in signal intensity, and this signal loss correlates with the decrease in exocrine function (Figures 13 and 14) [42, 43].

Figure 13.

T1w GRE fat-sat MRI scan comparing a normal pancreas (a), a mild CP (b) and an advanced CP (c), where the non-enhanced T1 intensity of the gland is gradually reduced according to the severity of CP.

Figure 14.

M, 70 yo. Evolution of CP few months (up) and few years (down) after necrotizing pancreatitis recovery in T2w HASTE sequence (a), unenhanced T1w GRE fat-sat (b), delayed-phase T1w GRE fat-sat (c) and MRCP (d). The progressive upstream dilatation of the ductal system is accompanied by a progressive reduction of T1 intensity of the parenchyma which is increasingly replaced by fibrosis.

Moreover with “T1 mapping”, a novel advanced MRI technique, pancreatic T1 signal intensity may be reliably assessed and could be used as a practical and sensitive biomarker to monitor CP and to diagnose mild CP, even earlier than ductal anomalies become appreciable, as the fibrotic replacement of acinar cells precedes ductal alterations (Figure 15). T1 mapping is a quantitative MR imaging technique that allows measuring the tissue-specific T1 relaxation time. The T1 relaxation time of pancreatic parenchyma is significantly increased in patients with mild CP [44] and, given the quantitative nature of the data, T1 mapping may be a more reliable method compared to traditional T1 weighted imaging, allowing ready comparison across longitudinal time points and permitting a more meaningful interpretation of intensity changes, so it could become a biomarker. However, more studies are required to transform these potential benefits into clinical practice.

Figure 15.

M, 73 yo. Early-stage of CP in T1 mapping sequence (a), S-MRCP (b), T2w HASTE sequence c), unenhanced T1w GRE fat-sat (d). T1-mapping shows an increased T1 relaxation time of the gland even before the appearance of marked classic signs of chronic pancreatitis. S-MRCP visualization of side branches at body-tail after secretin is a sign of early CP.

After contrast injection, while a healthy pancreas typically displays strong enhancement in the arterial phase and homogeneously decreasing enhancement in the venous phase, in CP fibrotic tissue causes heterogeneously reduced enhancement in the arterial phase, followed by a delayed enhancement in the venous and equilibrium phase, related to the fibrotic changes of the pancreatic parenchyma (Figure 14) [28, 43].

The ductal abnormalities are well depicted on MRCP images. In particular, in the early-stage CP side branches get mildly dilatated and become visible, while in advanced stages are depicted more severe alterations of side branches (such as ectasia or sacculation) and alterations of the main duct such as irregular profiles, dilatation, focal strictures and filling defects (due to stones and protein plugs). Ductal abnormalities of CP can be scored according to the Cambridge Classification modified for MRCP (Table 2) [45].

Grading	Imaging findings
I (normal pancreas)	Pancreatic ducts are normal
II (equivocal pancreas)	1–2 side branches and main duct 2–4 mm
III (mild disease)	≥ 3 side branches and main duct 2–4 mm
IV (moderate disease)	≥ 3 side branches and main duct >4 mm
V (marked disease)	As above with one or more among large cavities (10 mm), gland enlargement (>2x), intraductal filling defects or calculi, duct obstruction, gross irregularity or contiguous organ invasion

Table 2.

Grading of chronic pancreatitis.

The overall sensitivity of MRCP for diagnosing CP increases from 77–89% using S-MRCP [46], which adds both morphological and functional information. Secretin infusion induces transitory hypertension in the ductal system improving the morphological evaluation of the main pancreatic duct and side branches and making eventual ducts anatomical variants (such as pancreas divisum), obstructions, stenosis, dilatations and irregular contours easier detectable.

In a healthy pancreas, ductal response to secretin stimulation determines an increase in the main duct caliber of approximately 1 mm with a peak at 3 min with the return to baseline caliber at 10 min. In CP periductal fibrosis causes a decrease in ductal compliance and leads to an abnormal and persistent main duct dilatation with visibility of the side branches. Thus, visualization of side branches at the body-tail after secretin is a sign of early CP (Figure 15) [47]. Moreover, in early stages of CP, secretin-induced hypertension may result in acinar filling with a progressive hydrographic enhancement of the pancreatic parenchyma, the so-called “S-MRCP parenchymogram” which is a sign of pancreatic outlet obstruction (Figure 16) [43, 48].

Figure 16.

M, 45 yo, Recurrent episodes of pain and increase of pancreatic enzymes. Pre-secretin MRCP (a) shows no significant changes. Just 2 minutes after secretin injection (b), an increase in signal intensity of the parenchyma can be observed and persists for the full 17 minutes of the exam (c). This phase shows a good passage of pancreatic juice in the duodenum due to adequate exocrine function.

Finally, S-MRCP allows to obtain a semiquantitative assessment of the duodenal filling which correlates with pancreatic exocrine function, with diagnostic performance comparable to that of invasive tests such as endoscopic pancreatic function testing [49]. The semiquantitative assessment is performed by applying a grading system to duodenal filling from grade I (filling limited to the duodenal bulb, indicating severely reduced duodenal filling), to grade II (filling visible as far as the second portion of the duodenum, indicating reduced duodenal filling),

to grade III (filling beyond the second portion of the duodenum, indicating normal duodenal filling); a reduced duodenal filling suggests a decrease in pancreatic exocrine reserve. However, the normal duodenal filling does not exclude impairment of pancreatic exocrine function; so reduced duodenal filling is a specific but not sensitive sign of CP.

In some cases, CP can be focal and thus simulates PDAC and differential diagnosis is very difficult, even for the pathologist, because PDAC is characterized by a rich desmoplastic component.

To make a correct diagnosis, the radiologist can rely both on morphological criteria (in the particular relationship between the lesion and the dilatated ducts, the relationship between the lesion and calcifications and enhancement criteria) and on functional criteria (in particularly advanced DWI techniques and S-MRCP).

In PDAC both pancreatic dilatated ducts and calcifications are displaced at the periphery of the lesion, while in focal CP calcification and dilatated ducts are part of the lesion and so are located within it.

Both focal CP and PDAC are hypointense in T1 fat-sat and hypovascular in the pancreatic arterial phase, but while PDAC most of the time persists hypovascular, in focal CP a delayed enhancement is often detected.

Both focal CP and PDAC cause stenosis of the main duct, however, while in focal CP the stenoses reduce or resolve after secretin stimulation (duct penetrating sign), it does not change in PDAC (Figure 17) [50].

Figure 17.

M, 65 yo. CP with evidence of two ductal strictures at MRCP sequences (arrows) at diagnosis (a) and a few months later (b). CT (c) performed two years later discovers multiple gross calcifications of pancreatic parenchyma, typical of CP.

As the risk of pancreatic cancer is significantly elevated in patients with CP (cumulative risk at 10 and 20 years after the diagnosis of pancreatitis, respectively 1.8 and 4% [40]), this population needs to be followed up also to early detect PDAC, when the lesion is still resectable. MRI with MRCP and eventually with s MRCP is the best technique to early detect PDAC since very often the first sign of PDAC onset is focal stenosis of the main duct that does not resolve after secretin stimulation.

In advanced CP, the aspect of the pancreatic ductal system may mimic that of the main duct intraductal papillary mucinous neoplasm (MD-IPMN); however in MD-IPMN the dilatation of the main duct is more homogeneous with regular margins and without strictures, usually associated with bulging ampulla, sometimes with grape-like secondary duct dilatation and with a solid nodule in a duct, while specific findings of CP are ductal dilatation with strictures, the presence of a stone and side branches ectasia with non-cystic appearance (Figure 18) [51].

Figure 18.

CP with multiple calcifications at CT scan (a) and diffuse dilatation of ductal system at MRCP (b), compared to a mixed IPMN with main duct IPMN component clearly visible at MRCP (c).

In conclusion, nowadays MRI is the best technique to early detect and monitor CP, to early detect PDAC in patients with CP and make a differential diagnosis between PDAC and focal CP and between MD-IPMN and CP. In the future MRI with T1 mapping could provide a biomarker to detect and monitor CP [52].

6.2 CT imaging

CT has been a cornerstone for evaluating CP, thanks to its availability and reliability. Even if MRI has superior accuracy for imaging the ductal system, CT with its high spatial can well depict both the parenchyma and the dilatated ducts in a few minutes and provides good-quality morphological information even in uncooperative patients; moreover, CT is the best technique to detect and study the structure of parenchymal and intraductal calcifications, and to identify CP complications such as pseudocysts, vascular thrombosis and pseudoaneurysm [52].

Unenhanced CT may be considered complementary to MRI and MRCP because it allows to easily identify and precisely localize both pancreatic parenchymal and ductal calcifications (important information for treatment planning) (Figure 19), and permits to study the structure of stones, in order to identify features suggestive of gene mutations associated with CP. In particular stones with a hypodense central core, with the so-called “bull’s eye” appearance, are detected in 67% of patients with a gene mutation associated CP [53] and identifying these patients is important because they have an even higher risk of developing PDAC and thus require strict surveillance, genetic counseling and family testing.

Figure 19.

M, 48 yo. Chronic calcific pancreatitis with multiple gross calcifications in the dilatated ductal system (a), invisible at MRCP sequence (b).

During the pancreatic parenchymal phase (a late arterial phase acquired approximately 40 s after the initiation of intravenous contrast injection) parenchymal enhancement is typically reduced in CP, due to fibrotic changes. Moreover, complications such as fluid collection and vascular abnormalities like pseudoaneurysms are detected. In the portal venous phase (70–90 s after intravenous contrast medium injection) venous vessels can be adequately studied and complications such as fluid collection and vascular abnormalities like thrombosis are detected [43].

Although CT represents a reliable technique to study patients with CP, it has some important limits. First of all, CT has low sensitivity to detect minimal pancreatic and ductal changes, thus a negative CT does not rule out an early/mild CP [54]. Moreover, CT causes patient exposure to ionizing radiations, which raises concerns for longitudinal monitoring in particular for younger patients, and finally it has rather low sensitivity (58–77%) to detect small iso-attenuating PDAC because of its non-optimal contrast resolution [55, 56].

7. Conclusion

Imaging of pancreatitis is complex. CT and MRI, also flanked by modern S-MRCP techniques and in the future by T1-mapping, allow their early differential diagnosis, the search for the underlying causes, guide the therapeutic path and the response to therapy, allowing careful follow-up.