EDITORIAL

nature publishing group

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PANCREAS

see related article on page 1780

Secretin-Enhanced MRCP:
Proceed With Cautious Optimism
Nisha I. Sainani, MD1 and Darwin L. Conwell, MD2

Abstract: Magnetic resonance imaging (MRI)

is a safe and universally available test that has
much appeal to generalists and subspecialists
evaluating patients with pancreatic disease.
Testoni et al. report the clinical utility of magnetic
resonance pancreaticocholangiography (MRCP)
and secretin-enhanced MRCP in the evaluation
of patients with asymptomatic abnormalities
in pancreatic enzymes. The authors report that
chronic pancreatitis changes will be seen in up to
a third of patients with asymptomatic elevations
in pancreas enzymes when compared with agematched controls. The changes described on MRI
and secretin-enhanced MRI are not in question,
but the clinical significance of these changes
is unknown. The authors rightly report that
some of the changes seen may be age related,
nonspecific, and of unknown clinical significance.
Any new imaging and diagnostic test needs to
be interpreted with caution until appropriate
prospective clinical trials have been performed.
It appears that secretin stimulation enhances the
diagnostic accuracy of MRCP for the detection
of minor changes in the pancreatic duct and
parenchyma. Gastroenterologists are encouraged to
proceed with cautious optimism when using MRI
for the evaluation of early chronic pancreatitis.
Am J Gastroenterol 2009; 104:17871789;
doi:10.1038/ajg.2009.168; published online 19 May 2009

Gastroenterologists are often evaluating patients with minimal abnormalities on routine serologic or imaging tests and
chronic abdominal pain of unknown origin (1). The diagnosis of early or minimal-change chronic pancreatitis is often
considered as a cause of this common clinical presentation
(2). It is widely accepted that the diagnosis of early chronic
pancreatitis remains difficult primarily because of a paucity
of pancreatic radiological abnormalities and the inability to
safely obtain histological biopsy (3). When the initial diagnostic evaluation is inconclusive, a referral is often made to
a tertiary center for advanced imaging, endoscopy, and pancreas secretory physiology testing. Patients evaluated at most
academic centers generally undergo a battery of studies
including various combinations of endoscopic ultrasound,
endoscopic retrograde pancreatography (ERCP), dynamic
pancreas computed tomography scan, magnetic resonance
imaging (MRI), and hormone-stimulated pancreas function tests. Currently, pancreas function tests and ERCP
are considered the most accurate methods and the nonhistologic, surrogate gold standards for the detection of
chronic pancreatitis (4). Although pancreatic function studies
have shown excellent diagnostic accuracy at detecting moderate chronic pancreatitis, they are not universally available,
and the invasiveness of ERCP has caused it to no longer be
used as a diagnostic modality. Thus, the search for a safe and
universal and readily available test to detect early chronic
pancreatitis continues (5).
MRI, with its better soft-tissue resolution and capability to visualize the ductal system by means of magnetic
resonance pacreaticocholangiography (MRCP), acquired
either as two-dimensional or three-dimensional images, has
emerged as a diagnostic tool to evaluate patients with suspected pancreatic disease (6). MRI has great appeal to generalists and subspecialists as it can evaluate the parenchymal
and ductal changes noninvasively, without radiation, and
does not cause procedure-related pancreatitis as its endoscopic equivalent, retrograde pancreatogram (ERCP), does.

Department of Radiology, Division of Abdominal Imaging and Intervention, Harvard Medical School, Brigham and Womens Hospital, Boston, Massachusetts,
USA; 2Department of Medicine, Center for Pancreatic Disease, Harvard Medical School, Brigham and Womens Hospital, Boston, Massachusetts, USA.
Correspondence: Darwin L. Conwell, MD, Cleveland Clinic, Gastroenterology, 9500 Euclid Ave., Cleveland, Ohio 44195, USA. E-mail: dconwell@partners.org
Received 28 January 2009; accepted 4 February 2009
2009 by the American College of Gastroenterology

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Sainani and Conwell

In addition, MRI does not usually require sedation analgesia or

referral to a tertiary center as would be required for advanced
endoscopic procedures such as endoscopic ultrasound, ERCP,
and hormone-stimulated pancreas function tests. Furthermore,
the addition of the hormonal stimulant secretin has enhanced
the diagnostic accuracy of MRCP by allowing better visualization of the pancreas ductal anatomy. In this issue of the American
Journal of Gastroenterology, Testoni et al. (7) and others report
the clinical utility of MRCP and secretin-enhanced (S-MRCP)
in the evaluation of patients with asymptomatic abnormalities
in pancreatic enzymes.
The investigators report a comparative study of 25 consecutive patients with chronic nonpathological pancreatic hyperenzymemia (CPH) and 28 consecutive age-matched controls
with recurrent upper abdominal pain and normal pancreatic enzymes. Both study groups underwent an MRCP and
S-MRCP. The authors found that S-MRCP showed abdominal pancreatic morphological findings in 13 of 25 CPH cases
(52%) and 1 of the 28 controls (3.6%, P < 0.001). The MRCP
findings were consistent with a diagnosis of early chronic
pancreatitis according to the Cambridge classification in
eight of the CPH cases (32%) after secretin injection but in
none of the controls. The investigators concluded that secretin
stimulation boosted the diagnostic yield of MRCP for the
diagnosis of chronic pancreatitis fourfold, uncovered findings
of pancreas divisum, and recognized persistent dilatation of
the main pancreatic duct. The investigators further stated that
S-MRCP detected ductal findings consistent with chronic pancreatitis in up to one-third of cases that have asymptomatic
elevation in pancreatic enzymes. In their opinion, S-MRCP
should be added to the evaluation of patients with asymptomatic pancreatic enzyme elevation for the diagnosis of early
chronic pancreatitis.
Due to the retroperitoneal location of the pancreas, the diagnosis of early chronic pancreatic disease requires highly specialized invasive procedures that carry a significant morbidity
and potential mortality. For example, ERCP is considered the
radiological gold standard at diagnosing chronic pancreatitis but carries a 515% risk of procedure-related acute
pancreas injury. And even the pancreatic function test, the nonhistological gold standard, is invasive and only used at a few
selected tertiary centers. These two procedures are the best surrogate gold standards as safe histological biopsy of a normalappearing pancreas is not practical. Despite these reference
standards, an alternate noninvasive method would be beneficial to the practicing clinician and have wider applicability.
Pancreatic MRI examination consists of acquiring various
MRI sequences through the upper abdomen using a torso
phased-array coil. A typical MR pancreas protocol involves
coronal T2-weighted (T2-W) fast spin echo (FSE), axial T2
FSE and single-shot FSE, axial T1-W inphase and outphase
(chemical-shift imaging for identification of fat), axial T1-W
fat-saturated images, and dynamic post-contrast axial T1-W
fat-saturated images in late arterial, portovenous, and equilibrium phase acquired through the upper abdomen. For MRCP,
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several two-dimensional, coronal, thick-slab (40 mm), heavily

T2-W images are acquired along the plane of pancreatic duct,
whereas for three-dimensional acquisition, coronal images,
thin-slice (1 mm), heavily T2-W images are acquired through
the pancreas from which maximum-intensity projection
images are reconstructed. For S-MRCP, the two-dimensional
acquisitions are repeated every 30 s for 10 min after intravenous administration of 0.2 mcg/kg body weight of secretin.
Pre- and post-secretin images are then compared for changes
in main pancreatic ductal caliber (compliance), better visualization of ductal segments and side branches, sphincter of
Oddi function, and duodenal filling. Secretin administration also increases the parenchymal signal intensity on T2-W
images.
In patients with moderate chronic pancreatitis, the pancreatic parenchyma shows abnormal high signal intensity on
T2-W images and low signal intensity on T1-W images with
delayed enhancement pattern after gadolinium administration. The presence of a signal-intensity ratio (signal intensity
in post-contrast divided by that in pre-contrast) of < 1.7 in the
arterial phase and/or delayed peak enhancement after contrast
administration has a sensitivity of 92% and a specificity of 75%
for the demonstration of early chronic pancreatitis. The secretin-induced pancreatic T2 signal-intensity changes are significantly reduced in patients with a mild exocrine pancreatic
insufficiency as compared with healthy volunteers. On MRCP,
fluid in the pancreatic and biliary ducts is seen as high signal
intensity because of heavily T2-W images. However, visualization of normal or minimally dilated pancreatic ducts by MRCP
is more challenging because of their small size (810). Secretin
administration stimulates fluid and bicarbonate secretion by
the exocrine pancreas; consequently, it improves the pancreatic duct and side-branch delineation and also allows evaluation of the exocrine pancreatic function. Side-branch ectasia,
mild ductal dilatation with loss of the normal gentle taper, and
mural irregularities are the pathognomonic MRCP features of
early-stage chronic pancreatitis. Through measurement of the
duodenal filling, S-MRCP allows quantitative assessment of the
exocrine pancreatic function. Thus, S-MRCP, when combined
with MRI of pancreas, furnishes anatomical and functional
information and enhances the diagnostic sensitivity of MRI for
evaluation of early chronic pancreatitis (11).
More recently, the role of diffusion-weighted (DW) MRI is
being investigated in evaluation of pancreatic pathologies. Utilizing diffusion-weighted imaging (DWI), studies have provided
some evidence for the cause of the difference in enhancement
on secretin-enhanced MRI of pancreas. DWI is based on intravoxel incoherent motion imaging that allows visualization of
molecular diffusion and microcirculation of the blood in the
capillary network (perfusion) of biological tissues. The DWI is
quantified by an apparent diffusion coefficient, which integrates
both diffusion and perfusion. The apparent diffusion coefficient
is equal to the true diffusion coefficient D, when diffusion is
the only type of motion present. In in vivo tissues, however,
the reported apparent diffusion coefficients have often higher
VOLUME 104 | JULY 2009 www.amjgastro.com

Editorial

2009 by the American College of Gastroenterology

CONFLICT OF INTEREST

Guarantor of the article: Darwin L. Conwell, MD.

Specific author contributions: Darwin L. Conwell: concept
and clinical details of the paper; Nisha Sainami: radiology
details of the paper.
Financial support: None.
Potential competing interests: None.
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PANCREAS

values than expected because of the effect of perfusion. Secretin has also been shown to increase pancreas blood flow and
perfusion. The increased mobility of the water molecules and
increased circulation in the capillaries of the pancreas might
be quantified through DWI. In general, increases in diffusion
and perfusion cause decreases in signal intensity on DW MR
images and increases in apparent diffusion coefficient values.
Several experimental flow measurement studies assessing pancreatic perfusion have shown that chronic pancreas fibrosis is
associated with a reduction in parenchyma perfusion. Therefore, DW may be able to recognize pancreatic fibrosis/chronic
pancreatitis. In fact, a recent publication has shown that DWI
has promise as a noninvasive method to assess pancreas exocrine function in chronic pancreatitis (12).
The initial excitement of any new imaging and diagnostic
test needs to be interpreted with caution until the appropriate
prospective clinical trials have been performed to determine
its true accuracy and clinical efficacy. Furthermore, experience
with the test over time generally will determine its true role as
it is applied to the clinical care of patients with various presentations. In addition, MRCP reports need to be standardized
and to document findings in a systematic and regimented protocol that is universally accepted. Similar excitement had been
reported earlier in the initial experience with endoscopic ultrasonography only to find out that at least five criterianot three
criteria as initially reportedare needed to make a definitive
diagnosis of chronic pancreatitis (1315). These facts should be
kept in mind when interpreting MRI findings in the evaluation
of early chronic pancreatitis.
In conclusion, on the basis of this investigation and findings
by others, it appears that S-MRCP improves visualization of the
pancreatic ducts and detects morphological changes that have
been ascribed earlier to patients with chronic pancreatitis. But
caution needs to be exercised when trying to interpret these
structural abnormalities. As the investigators rightly report,
some of the changes may be age related, nonspecific, and of
unknown clinical significance. Although secretin-enhanced
MRI is an exciting technological advance, and most pancreatologists believe it should be considered in the evaluation of
patients with perplexing signs and symptoms suggestive of early
pancreatic disease, prospective comparison trials with a reference standard test or long-term follow-up are clearly needed.
And in fact, a multicenter trial is currently under way and we
await the results of this study with cautious optimism.

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