Richenel T. 0. Tjon A Tham, Aeilko H. Zwinderntan, PhD Wim Bakker, MD #{149} Comnelis
Cystic
MD
G. M. Heyerman, L Bloem, MD B. H. W. Lamers, MD
Fibrosis:
MR Imaging
The appearance of the pancreas in 17 adult patients with cystic fibrosis was evaluated with magnetic nesonance (MR) imaging. The pancreas was abnormal in 15 patients. Three patterns were observed: (a) lobulated enlarged pancreas with complete replacement by fatty tissue (n 9), (b) small atrophic pancreas with partial replacement by fat tissue (n = 5), and (c) diffuse atrophy of the pancreas without fatty replacement (n = 1). Replacement of the pancreas by fat tissue was seen on Ti-weighted images with, characteristically, a very high signal intensity. The sensitivity of MR imaging in depicting pancreatic abnormality in cystic fibrosis is 94%, which is comparable to that of computed tomography. Index
terms:
cneas, CT, 770.1496 Radiology
Fibrosis, cystic, 770.1496 770.121 1 #{149} Pancreas, diseases, #{149} Pancreas, MR studies, 770.1214 1991;
#{149} Pan-
179:183-186
From the Departments of Diagnostic Radiology (R.T.O.T.A.T., T.H.M.F., J.L.B.), Pulmonology (H.G.M.H., W.B.), Medical Statistics (A.H.Z.), and Gastroenterology and Hepatology (C.B.H.W.L.), University Medical Centre
Leiden,
Cathanina
Ziekenhuis,
#{149} Harry
MD
#{149} Theo
H. M. Falke,
MD
#{149} Johannes
C
of the
fibrosis (CF) may be defined as a congenital familial disease characterized by dysfunction of many of the exocnine glands; the most obvious signs of CF are chronic bnonchopulmonary infectious, malabsorption secondary to pancreatic insufficiency, and a raised sweat sodium concentration (1-3). The extent of respiratory involvement is easier to assess than the cxtent of pancreatic disease. Sonography and computed tomography (CT) have been used to assess the involvement of the pancreas in CF. In cases in which the pancreas has been meplaced by fat tissue, sonognaphy shows an increased homogeneous or inhomogeneous echogenicity with a normal-sized or small pancreas (4). However, sonography is not sensitive enough to enable the detection and estimation of the extent of the morphologic changes, and false-negative sonograms have been reported (4-6). On the other hand, CT is highly sensitive in showing pancreatic morphobogic abnormalities in CF, but it has the disadvantage of using ionizing radiation in this group of usually young patients. Magnetic resonance (MR) imaging provides a noninvasive method with the advantage of not using ionizing radiation. To our knowledge, there has not been a study that has systematically analyzed the MR imaging findings of pancreatic abnormalities in CF (4,7). We present MR imaging as a technique that enables a reliable visualization of the pancreatic changes in CF. The spectrum of MR imaging features of the pancreas in CF, correlated with CT and clinical findings, is described. YSTIC
Michelangelo-
laan 2, P0 Box 1350, 5602 ZA Eindhoven, The Netherlands. Received June 26, 1990; revision requested August 27; revision received October 1; accepted November 29. Address reprint requests to R.T.O.T.A.T. CRSNA, 1991
MATERIALS
AND
METHODS
We studied 17 adult patients with cystic fibrosis (eight women, nine men); ages ranged from 18 to 43 years (mean, 29
Pancreas’ years ± 7). All patients had moderate to severe pulmonary disease. Fourteen patients had exocrine pancreatic insufficiency, which was determined by having a fat excretion of more than 10% (8,9). They were treated with pancrelipase (Pancrease; Cilag, Herentals, Belgium). Two patients with pancreatic insufficiency also had diabetes mellitus, which icquired insulin. Three patients had normal pancreatic function. Eight of the 14 patients with exocrine pancreatic insufficiency were examined with both CT and MR imaging, six underwent only MR imaging. The three patients with normal pancreatic function underwent only MR imaging. Twenty-seven ageand sex-matched control
subjects
without
gastrointestinal
disorders served as a control group for the MR imaging studies. All MR images were obtained with a Gyroscan S5 (Philips, Eindhoven, The Netherlands), and imaging was initially performed
with
9-10-mm-thick
trans-
verse sections with Ti- and T2-weighted techniques. Ti-weighted images with 9iO-mm-thick
coronal
sections
were
also
obtained. All MR imaging was performed at 0.5 T with use of a body coil. The following imaging parameters were used: multisection acquisition, a 2-mm intersec-
tion gap, a 179 X 256 or i28 X 256 acquisition matrix, and a 256 X 256 display matrix. The field of view varied between 300 and 400 mm. Pulse sequences used were spin-echo 300/20 (repetition time msec/ echo time msec) and 2,000/50-100. Water was orally administered as the contrast medium (500 mL) before each MR imaging examination; then, 1 mg of glucagon was intravenously administered to reduce bowel peristalsis. The CT examinations were performed with a Tomoscan 350 (Philips, Eindhoyen, The Netherlands), and routine scans were repeatedly obtained after intravenously
administered
bolus
injection
of
120 mL of meglumine ioxitalamate (Telebrix 38; Andre Guerbet, Aulnay-sousBois, France). A contrast medium (10 mL of Telebnix diluted in 500 mL of water) was orally administered routinely before each CT examination.
Abbreviation:
CF
=
cystic
fibrosis. 183
-
‘
1
/,,..
.,
..
,-
b.
a.
Figure
(a) CT scan
1.
of a 27-year-old
man
with
C.
CF with
placement
of the pancreas (arrows) by hypentrophic fat patient was receiving pancreatic enzyme supplementation. homogeneous very high signal intensity. There is good
weighted
image
MR
To determine
(2,000/50)
the
usefulness of tion of disease
of the pancreas
sensitivity
and
MR imaging in of the pancreas,
the
with
tients
and
tient.
CT
with and
findings
autopsy
data
MR
retrospectively eight
clinical imaging
CT
was
in one findings
correlated
patients;
in all
in the not
performed
pa-
pawere
first in
the
remaining patients. Size and signal intensity or attenuation of the pancreas were evaluated for MR and CT images. Signal intensity or attenuation of the pancreas was assessed relative to the liver, subcutaneous fat, and spleen and was calculated from a region of interest of at least 1 cm2 in size. Statistical analysis was performed with correlation analysis and analysis of vanance tests. P values less than .05 were considered significant. Interobserver vanance was measured by means of the correlation coefficient and Cohen ic.
which
The
CT
scans
and
typical
bobulated
images
insufficiency. Two of the three patients without exocnine pancreatic insufficiency had normal MR findings, the third had a fatty pancreas at MR imaging.
184
#{149} Radiology
replaced
patterns
fuse
“dark”
by fat tissue
with
of pancreatic
pancreas
attenuation
with
similar
steatorrhea
shows
a high
signal
intensity.
,
the
of tissue could
00
1.2
of fat
1.0
0.S
.
0.G 0.4
bright
nine
pancreas.
of the
ratio, 1.78septations or
with a lower be appreciated
This
17 patients
was
(53%)
2%-5i%)
crate-sized
as a small
pancreas
with,
tissue
signal varied
(Fig
pattern
The
ratio 1.18
was
CF
CF
vith
vithout s*nihoet
sWtnbo.e
2.
Signal on
within seen in
(300/20) in control subjects (n 27) and patients with CF with (n 14) or without (n 3) steatorrhea. Patients with diabetes mellitus that required insulin are denoted by an
(95%
intensity Ti-weighted
ratio
of
pancreas
MR images
asterisk.
seen by
tis-
or mod-
predomi-
with-
of the
pancreas-liver in this group and 2.18.
seen
subject,
liver
be seen
intensity
3b).
intensity between
A third
could
signal
coRtol
versus
nantly, a very high signal intensity on the Ti-weighted MR images. Intemmediate signal intensity of the high
0.0
Figure
sue with similar attenuation to that of fat (Fig 3a). The degree of fatty meplacement varied in the patients, and it was focally more pronounced in one part of the pancreas than in the other. This pattern was visualized in five patients (29%) (95% confidence interval,
0.2
signal
confidence interval, 29%-77%). The second pattern we noticed was partial replacement of the pancreas by fat tissue. This pattern was on CT scans as a focal or diffuse atrophic pancreas surrounded
0
1.4
cal hypentrophic and lobulated pancreas with high signal intensity due to very high signal intensity from the
streaks intensity
re-
4.
(Fig ia). Tishowed a typi-
fat tissue (pancreas-liver i.84) (Figs lb. 2). Subtle
complete
2.6
dif-
to that
and discrete septations weighted MR images
pancreas MR
is entirely
and
of low attenuation; there are no signs of atrophy. The MR image (300/20) of the pancreas (arrows) shows changes seen on the CT scan. (c) Transverse T2-
as by fat tissue. This was visualized on CT scans as a hypemtnophic and
in the
showed morphologic changes in all 14 patients with exocnine pancreatic
symptoms
changes from CF could be identified. The most common pattern seen was complete replacement of the pancre-
pancreatic RESULTS
gastrointestinal
which is seen as an area (b) Transverse Ti-weighted correlation with the morphologic
Three
examinations were retindependently scored in a blind fashion by two radiologists (T.H.M.F. and J.L.B.) without knowledge of clinical information. If CT was performed, this scan was shown to the meviewers separately from the MR image. The MR images and CT scans of the patients with CF were scored as part of a blind study of 135 subjects, which included 94 patients with pancreatic disease, 20 control patients with diseases not related to the pancreas, liver, or digestive tract, and 21 healthy volunteers. The images were evaluated for the presence of abnormalities of the liver, bile ducts, gallbladder, pancreas, spleen, and portal venous system. The MR imaging observations were
and
tissue,
(arrows),
the
detecthe CT
and MR imaging rospectively and
correlated
pulmonary
in one
pa-
tient (6%) (95% confidence interval, 0%-i8%) who showed complete atrophy of the pancreas at CT without fatty replacement (Fig 4a). MR im-
ages of this patient showed atrophy of the pancreas with a signal intensi-
ty comparable to that of the liver (Fig 4b, 4c) (Ti pancreas-liver ratio, 0.8i; T2 [2,000/50-iOO} ratio, 0.70-0.96). Both complete and partial replacement of pancreatic tissue by fatty tissue could be clearly visualized on the Ti-weighted transverse and coronal sections (Fig 3c). Only one patient without signs of exocrine pancreas insufficiency demonstrated partial replacement of the pancreas by fat tissue at MR imaging. The two patients with exocnine pancreatic insufficiency and manifest diabetes mdlitus that required insulin therapy showed different morphologic pattemns. One showed partial fatty meplacement, while the other had cornplete atrophy of the pancreas without fatty replacement (Figs 2, 4). The changes on the T2-weighted
MR images
(Fig
ic) of the
patients
with seen
CF were less striking than those on the Ti-weighted images (Fig 5). In the patients with complete meplacement of the pancreas by fat tis-
April
1991
.
.
, ;
1
.
t
4
‘
v
,
/
‘
\, .
‘t
‘
*
,
i
I
----.-
b. Figure creatic
3. (a) Transverse CT scan of a 24-year-old enzyme supplementation. CT scan shows
.
C.
woman with CF with pulmonary and gastrointestinal symptoms. a small pancreas (arrows) with partial replacement of the pancreas
She was receiving panby fat tissue. (b) Trans-
verse Ti-weighted MR image (300/20) of a small pancreas (arrows) with an inhomogeneous signal intensity caused by the high sity of fat tissue and the intermediate signal intensity of residual pancreatic tissue. (c) Coronal Ti-weighted MR image (300/20) creas (arrows) shows inhomogeneous high signal intensity. The small pancreas shows focal areas of intermediate signal intensity pancreatic tissue that has not been replaced by fat tissue and larger areas of high signal intensity from fat tissue.
Figure
(a) Transverse
4.
CT scan
of
a 27-year-old
woman
with
CF
with
pulmonary
and
gastrointestinal
symptoms.
She was
signal of the from
treated
intenpanthe
with
pancreatic enzyme supplementation and received insulin for diabetes mellitus. CT scan shows complete atrophy of the pancreas (arrows), which shows normal attenuation. There are no signs of replacement of the pancreas by fat tissue. Transverse Ti- (300/20) (b) and T2- (2,000/ 100) (c) weighted MR images demonstrate an atrophic pancreas (arrows) with the same signal intensity as that of the liver.
2.6
T2 Relaxation
2.4
Times
in Control
Subjects
and
Patients
with
T2 Relaxation 00
1.S
Patients
1.6
S
1.4
.
1.2 1.0
with
0
S
Liven Normal
0
*
y
Abnormal
.
0.2 0.0
*
control sibjcu
CF vith
Significantly
(msec)
. .
Subjects
66.64±15.11 68.52
± 12.07
pancreas
All patients with CF Patients with CF with steatonrhea Patients with CF without steatorrhea
0.6 0.4
Time
Control CF
96.37±31.86k pancreas
CF
different
(P < .05) from
that
92.35 97.44 71.98 of control
± 40.72* ± 44.36 ± 2.28
... ... ...
subjects.
CF
vltit
asunr.bo.s
Figure
5. The pancreas-liver signal intensity ratio on T2-weighted MR images (2,000/ 100) in control subjects (n 27) and patients with CF with (n i4) and without (n 3) steatorrhea. Patients with diabetes mellitus who
required
insulin
are denoted
by an as-
tenisk.
sue, the signal intensity was moderate to very high (pancreas-liver ratio, 1.62-2.03; mean, 1.83) on the T2weighted
Volume
images
179
(2,000/50)
Number
#{149}
1
(Fig
ic)
but moderately high (pancreas-liver ratio, 1.29-i.80; mean, 1.55) on the T2-weighted images (2,000/ 100). In patients with partial fatty replacement of the pancreas, the T2-weighted images showed no typical pattern. The T2 relaxation times were significantly longer (P < .05) for the pancreas and liver of the patients with CF (Table). In our study, water was orally administered as a contrast medium to
delineate and bowel
the pancreas from stomach loops. In patients with fatty replacement of the pancreas, this resulted in excellent contrast on the Ti-weighted images. However, the delineation was less clear on the T2weighted images. There was complete agreement in interpretation of the MR images and CT scans by both radiologists. Theme were no false-negative findings. There was, however, one false-posi-
Radiology
185
#{149}
tive finding for a patient with CF without steatorrhea. Quantification of the agreement between the two coefficient of .95 and a Cohen K of 0.95 (standard error, 0.15). MR imaging and CT had similar sensitivities (94%) and specificities (100%). The positive predictive value was 100% and the observers
resulted
negative
in a correlation
predictive
value
was
96%
for both modalities. There was a statistically significant difference between the signal intensity ratio of pancreas and liven and between pancreas and subcutaneous fat in patients with CF and in control subjects. No difference in size of the pancreas was noted in patients with CF on in the control subjects. There was, however, indication that the pancreas was enlarged in patients with complete fatty replacement of the pancreas. Additional findings at MR imaging and CT included hepatosplenomegaly (n 4), hepatomegaly (n = 3), splenomegaly (n 1), cholelithiasis (n 1), sludge (n 1), micmogallbladden (n 2), and renal calculi (n = 1).
In this series, pancreatic involvement by CF had three appearances on MR images: (a) lobulated enlarged pancreas with complete fatty replacement corresponding to lipomatous pseudohypemtrophy (this is seen as an enlarged pancreas with high signal intensity on both Ti- and T2-weighted images) (Fig i) (10); (b) atrophied fatty pancreas with variable degrees of fibrofatty meplacement (Fig 3) (4,7) (this is seen as a small pancreas with an inhomogeneous high signal intensity on the Ti-weighted images due to the abundant amount of fat tissue scattered between atrophic pancreatic tissue); and (c) atrophied pancreas without fatty replacement (Fig 4) (only atrophy is seen on MR images, and there is no change in signal intensity on the Ti- and T2-weighted images).
A fourth pattern, described in the biterature although not present in this series, is pancreatic cystosis, which meflects cyst formation due to inspissated Pancreatic
cystosis,
which
has been reported to be suggestive of complete cystic transformation of the pancreas, shows the same morphologic appearances on CT scans and MR images as the cases that are described as Iipomatous pseudohypertrophy (10,11) (Fig i). It is suggested that it represents one end of the spectrum of the pancreatic disease in CF-true cysts that eventually
undergo
that become mality (10).
186
#{149} Radiology
depicting
fatty
liposclemotic
the predominant
changes
abnor-
infiltration
of the
pan-
creas, while the opposite is true for depicting gallbladder disease (7). The pancreas morphologic
could
be easily analyzed changes and, in this
for
study, there was good correlation with the CT findings of the pancreas with a high sensitivity (94%) and specificity (100%) for MR imaging. The main disadvantage of MR imaging was the inability to show the small calcifications in the kidneys, pancreas, and gallstones that may be found in CF (7,13). Hepatosplenomegaly with signs of portal hypertension with or without varices and a microgallbladdem were additional findings at MR imaging (14). Theme is a broad spectrum of severity of clinical and morphologic findings in pancreatic
DISCUSSION
secretions.
All patterns described are the result of precipitation of relatively insoluble proteins, which causes obstruction of the small pancreatic ducts. This precipitation is related to the low water content of the ductal fluid caused by the impaired anion transport in CF (i2). The high signal intensity of the fatty pancreas on MR images is due to the short Ti relaxation time of the protons in fat (Table). MR imaging is considered to be superior to sonography in
and
hepatic
changes
function
tests
(16).
tients
function
in
these
pa-
be normal. However, the deof pancreatic tissue in these patients may be considerable because exocnine pancreatic insufficiency occurs only when more than 98%-99% of the entire pancreas is damaged (12). In this small group of patients, MR imaging may help detect the extent of destruction and give an indication for the development of exocnine pancreatic insufficiency that is related to the prognosis of the patient. Other causes of fatty replacement with atrophy of the pancreas include main pancreatic duct obstruction, malnutrition, Schwachman syndrome, hemochmomatosis, and viral infection (17,18). Cushing syndrome and steroid therapy may cause reversible fatty infiltration of the pancreas. Rarely, multiplc nodular fatty masses may cause the pancreas to become enlarged; this is descnibed as lipomatous pseudohypemtrophy of the pancreas (10). At histologic examination, fibrofatty replacestruction
may
tests
with
can
in such
be seen
changes
are similar
experimentally
preservation
of
cases.
to those
These
produced
by ligature
of the
main
pancreatic duct (i7,i8). The fatty meplacement and atrophy in CF are probably the result of this same mechanism and
are
caused
by protein
plug
obstruc-
tion
of acinar and larger pancreatic ducts. The degree of fat replacement and atrophy could be related to the severity of expression of CF in the mdividual patients, which results in various degrees
of pancreatic
duct
obstruction.
No correlation could be established tween the severity of pulmonary pancreatic involvement. U
beand
References 1.
Fernald
2.
Lloyd-Still
3.
Abramson SJ, Baker DH, Amodio WE. Gastrointestinal manifestations fibrosis. Semin Roentgenol 1987;
4.
Fiel SB, Friedman AC, Caroline DF, Radecki PD, Faenber E, Grumbach K. Magnetic resonance imaging in young adults with cystic fibrosis. Chest 1987; 91:181-184. McHugo JM, McKeown C, Brown MT, Weller P. Shah KJ. Ultrasound findings in children with cystic fibrosis. Br J Radiol 1987; 60:137141.
view. Boston:
5.
6.
7.
GW,
Boat
Semin John
TF.
Cystic
Roentgenol JD.
1987;
Textbook
Wright,
fibrosis:
over-
22:87-96.
of cystic
fibrosis.
1983.
Willi UV, Reddish JM, brosis: its characteristic
JB, Bendon of cystic 22:97-113.
Teele RL. appearance
Cystic fion ab-
dominal sonography. AJR 1980; 134:10051010. Gooding CA. Lallemand DP, Brasch RC, Wesbey GE. Davis B. Magnetic resonance imaging in cystic fibrosis. J Pediatn 1984; 105:384388.
8.
9.
A minor-
ity of patients with CF (iO%-i5%) have no clinical sign of exocnine pancreatic dysfunction, and results of indirect pancreatic
of the acini
islets
in pa-
tients with CF (15). Morphologic findings of the pancreas vary from atrophy and fibrosis to complete fatty replacement of the entire pancreas. Diffuse fatty replacement occurs more often in older patients and represents an endstage disease of the pancreas (16). Up to this stage, theme is no correlation between histomomphologic findings and pancreatic
ment
10.
1 1.
Van de Kamer JH, ten Bokkei Huinink H, Weyers HA. Rapid method for the determination of fat in faeces. J Biol Chem 1949; 177:347-355. Lamers CBHW, Jansen JBMJ, Hafkenscheid JCM. Jongenius CH. Evaluation of exocnine and endocrine pancreatic function in older patients with cystic fibrosis. Pancreas 1990; 5:65-69. Nakamara N, Katanda N, Sakalibara A, et al. Huge lipomatous pseudohypertrophy of the pancreas. Am J Gastroenterol 1979; 72:171174. Hernanz-Schulman M, Teele RL, PerezAtayde A. et al. Pancreatic cystosis in cystic fibrosis.
12. 13. 14.
15.
16.
Radiology
1986;
158:629-631.
Dune PR, Forstner GG. Pathophysiology of the exocnine pancreas in cystic fibrosis. J Soc Med 1989; 82(suppl 16):2-10. lannaccone G, Antonelli M. Calcification of the pancreas in cystic fibrosis. Pediatn Radiol 1980; 9:85-89. Wilson-Sharp C. Irving HC, Brown RC, Chalmers DM, Littlewood JM. Ultrasonography of the pancreas. liver, and biliary system in cystic fibrosis. Arch Dis Child 1984; 59:923926. Green OC. Endocrinological complications associated with cystic fibrosis. In: Lloyd-Still JD. ed. Textbook of cystic fibrosis. Boston: John Wright, 1983; 329-349. Daneman A, Gaskin K, Martin DJ, Cutz E. Pancreatic changes in cystic fibrosis: CT and sonographic appearances. AIR 1983; 141:653655.
17. 18.
Partel 5, Bellon EMN. Haaga J. Park CH. Fat replacement of the exocnine pancreas. AJR 1980; 135:843-845. Robbins 5;. Pathologic basis of disease. Philadelphia: Saunders. 1974; 1056-1077.
April
1991
Cystic
MD
G. M. Heyerman, L Bloem, MD B. H. W. Lamers, MD
Fibrosis:
MR Imaging
The appearance of the pancreas in 17 adult patients with cystic fibrosis was evaluated with magnetic nesonance (MR) imaging. The pancreas was abnormal in 15 patients. Three patterns were observed: (a) lobulated enlarged pancreas with complete replacement by fatty tissue (n 9), (b) small atrophic pancreas with partial replacement by fat tissue (n = 5), and (c) diffuse atrophy of the pancreas without fatty replacement (n = 1). Replacement of the pancreas by fat tissue was seen on Ti-weighted images with, characteristically, a very high signal intensity. The sensitivity of MR imaging in depicting pancreatic abnormality in cystic fibrosis is 94%, which is comparable to that of computed tomography. Index
terms:
cneas, CT, 770.1496 Radiology
Fibrosis, cystic, 770.1496 770.121 1 #{149} Pancreas, diseases, #{149} Pancreas, MR studies, 770.1214 1991;
#{149} Pan-
179:183-186
From the Departments of Diagnostic Radiology (R.T.O.T.A.T., T.H.M.F., J.L.B.), Pulmonology (H.G.M.H., W.B.), Medical Statistics (A.H.Z.), and Gastroenterology and Hepatology (C.B.H.W.L.), University Medical Centre
Leiden,
Cathanina
Ziekenhuis,
#{149} Harry
MD
#{149} Theo
H. M. Falke,
MD
#{149} Johannes
C
of the
fibrosis (CF) may be defined as a congenital familial disease characterized by dysfunction of many of the exocnine glands; the most obvious signs of CF are chronic bnonchopulmonary infectious, malabsorption secondary to pancreatic insufficiency, and a raised sweat sodium concentration (1-3). The extent of respiratory involvement is easier to assess than the cxtent of pancreatic disease. Sonography and computed tomography (CT) have been used to assess the involvement of the pancreas in CF. In cases in which the pancreas has been meplaced by fat tissue, sonognaphy shows an increased homogeneous or inhomogeneous echogenicity with a normal-sized or small pancreas (4). However, sonography is not sensitive enough to enable the detection and estimation of the extent of the morphologic changes, and false-negative sonograms have been reported (4-6). On the other hand, CT is highly sensitive in showing pancreatic morphobogic abnormalities in CF, but it has the disadvantage of using ionizing radiation in this group of usually young patients. Magnetic resonance (MR) imaging provides a noninvasive method with the advantage of not using ionizing radiation. To our knowledge, there has not been a study that has systematically analyzed the MR imaging findings of pancreatic abnormalities in CF (4,7). We present MR imaging as a technique that enables a reliable visualization of the pancreatic changes in CF. The spectrum of MR imaging features of the pancreas in CF, correlated with CT and clinical findings, is described. YSTIC
Michelangelo-
laan 2, P0 Box 1350, 5602 ZA Eindhoven, The Netherlands. Received June 26, 1990; revision requested August 27; revision received October 1; accepted November 29. Address reprint requests to R.T.O.T.A.T. CRSNA, 1991
MATERIALS
AND
METHODS
We studied 17 adult patients with cystic fibrosis (eight women, nine men); ages ranged from 18 to 43 years (mean, 29
Pancreas’ years ± 7). All patients had moderate to severe pulmonary disease. Fourteen patients had exocrine pancreatic insufficiency, which was determined by having a fat excretion of more than 10% (8,9). They were treated with pancrelipase (Pancrease; Cilag, Herentals, Belgium). Two patients with pancreatic insufficiency also had diabetes mellitus, which icquired insulin. Three patients had normal pancreatic function. Eight of the 14 patients with exocrine pancreatic insufficiency were examined with both CT and MR imaging, six underwent only MR imaging. The three patients with normal pancreatic function underwent only MR imaging. Twenty-seven ageand sex-matched control
subjects
without
gastrointestinal
disorders served as a control group for the MR imaging studies. All MR images were obtained with a Gyroscan S5 (Philips, Eindhoven, The Netherlands), and imaging was initially performed
with
9-10-mm-thick
trans-
verse sections with Ti- and T2-weighted techniques. Ti-weighted images with 9iO-mm-thick
coronal
sections
were
also
obtained. All MR imaging was performed at 0.5 T with use of a body coil. The following imaging parameters were used: multisection acquisition, a 2-mm intersec-
tion gap, a 179 X 256 or i28 X 256 acquisition matrix, and a 256 X 256 display matrix. The field of view varied between 300 and 400 mm. Pulse sequences used were spin-echo 300/20 (repetition time msec/ echo time msec) and 2,000/50-100. Water was orally administered as the contrast medium (500 mL) before each MR imaging examination; then, 1 mg of glucagon was intravenously administered to reduce bowel peristalsis. The CT examinations were performed with a Tomoscan 350 (Philips, Eindhoyen, The Netherlands), and routine scans were repeatedly obtained after intravenously
administered
bolus
injection
of
120 mL of meglumine ioxitalamate (Telebrix 38; Andre Guerbet, Aulnay-sousBois, France). A contrast medium (10 mL of Telebnix diluted in 500 mL of water) was orally administered routinely before each CT examination.
Abbreviation:
CF
=
cystic
fibrosis. 183
-
‘
1
/,,..
.,
..
,-
b.
a.
Figure
(a) CT scan
1.
of a 27-year-old
man
with
C.
CF with
placement
of the pancreas (arrows) by hypentrophic fat patient was receiving pancreatic enzyme supplementation. homogeneous very high signal intensity. There is good
weighted
image
MR
To determine
(2,000/50)
the
usefulness of tion of disease
of the pancreas
sensitivity
and
MR imaging in of the pancreas,
the
with
tients
and
tient.
CT
with and
findings
autopsy
data
MR
retrospectively eight
clinical imaging
CT
was
in one findings
correlated
patients;
in all
in the not
performed
pa-
pawere
first in
the
remaining patients. Size and signal intensity or attenuation of the pancreas were evaluated for MR and CT images. Signal intensity or attenuation of the pancreas was assessed relative to the liver, subcutaneous fat, and spleen and was calculated from a region of interest of at least 1 cm2 in size. Statistical analysis was performed with correlation analysis and analysis of vanance tests. P values less than .05 were considered significant. Interobserver vanance was measured by means of the correlation coefficient and Cohen ic.
which
The
CT
scans
and
typical
bobulated
images
insufficiency. Two of the three patients without exocnine pancreatic insufficiency had normal MR findings, the third had a fatty pancreas at MR imaging.
184
#{149} Radiology
replaced
patterns
fuse
“dark”
by fat tissue
with
of pancreatic
pancreas
attenuation
with
similar
steatorrhea
shows
a high
signal
intensity.
,
the
of tissue could
00
1.2
of fat
1.0
0.S
.
0.G 0.4
bright
nine
pancreas.
of the
ratio, 1.78septations or
with a lower be appreciated
This
17 patients
was
(53%)
2%-5i%)
crate-sized
as a small
pancreas
with,
tissue
signal varied
(Fig
pattern
The
ratio 1.18
was
CF
CF
vith
vithout s*nihoet
sWtnbo.e
2.
Signal on
within seen in
(300/20) in control subjects (n 27) and patients with CF with (n 14) or without (n 3) steatorrhea. Patients with diabetes mellitus that required insulin are denoted by an
(95%
intensity Ti-weighted
ratio
of
pancreas
MR images
asterisk.
seen by
tis-
or mod-
predomi-
with-
of the
pancreas-liver in this group and 2.18.
seen
subject,
liver
be seen
intensity
3b).
intensity between
A third
could
signal
coRtol
versus
nantly, a very high signal intensity on the Ti-weighted MR images. Intemmediate signal intensity of the high
0.0
Figure
sue with similar attenuation to that of fat (Fig 3a). The degree of fatty meplacement varied in the patients, and it was focally more pronounced in one part of the pancreas than in the other. This pattern was visualized in five patients (29%) (95% confidence interval,
0.2
signal
confidence interval, 29%-77%). The second pattern we noticed was partial replacement of the pancreas by fat tissue. This pattern was on CT scans as a focal or diffuse atrophic pancreas surrounded
0
1.4
cal hypentrophic and lobulated pancreas with high signal intensity due to very high signal intensity from the
streaks intensity
re-
4.
(Fig ia). Tishowed a typi-
fat tissue (pancreas-liver i.84) (Figs lb. 2). Subtle
complete
2.6
dif-
to that
and discrete septations weighted MR images
pancreas MR
is entirely
and
of low attenuation; there are no signs of atrophy. The MR image (300/20) of the pancreas (arrows) shows changes seen on the CT scan. (c) Transverse T2-
as by fat tissue. This was visualized on CT scans as a hypemtnophic and
in the
showed morphologic changes in all 14 patients with exocnine pancreatic
symptoms
changes from CF could be identified. The most common pattern seen was complete replacement of the pancre-
pancreatic RESULTS
gastrointestinal
which is seen as an area (b) Transverse Ti-weighted correlation with the morphologic
Three
examinations were retindependently scored in a blind fashion by two radiologists (T.H.M.F. and J.L.B.) without knowledge of clinical information. If CT was performed, this scan was shown to the meviewers separately from the MR image. The MR images and CT scans of the patients with CF were scored as part of a blind study of 135 subjects, which included 94 patients with pancreatic disease, 20 control patients with diseases not related to the pancreas, liver, or digestive tract, and 21 healthy volunteers. The images were evaluated for the presence of abnormalities of the liver, bile ducts, gallbladder, pancreas, spleen, and portal venous system. The MR imaging observations were
and
tissue,
(arrows),
the
detecthe CT
and MR imaging rospectively and
correlated
pulmonary
in one
pa-
tient (6%) (95% confidence interval, 0%-i8%) who showed complete atrophy of the pancreas at CT without fatty replacement (Fig 4a). MR im-
ages of this patient showed atrophy of the pancreas with a signal intensi-
ty comparable to that of the liver (Fig 4b, 4c) (Ti pancreas-liver ratio, 0.8i; T2 [2,000/50-iOO} ratio, 0.70-0.96). Both complete and partial replacement of pancreatic tissue by fatty tissue could be clearly visualized on the Ti-weighted transverse and coronal sections (Fig 3c). Only one patient without signs of exocrine pancreas insufficiency demonstrated partial replacement of the pancreas by fat tissue at MR imaging. The two patients with exocnine pancreatic insufficiency and manifest diabetes mdlitus that required insulin therapy showed different morphologic pattemns. One showed partial fatty meplacement, while the other had cornplete atrophy of the pancreas without fatty replacement (Figs 2, 4). The changes on the T2-weighted
MR images
(Fig
ic) of the
patients
with seen
CF were less striking than those on the Ti-weighted images (Fig 5). In the patients with complete meplacement of the pancreas by fat tis-
April
1991
.
.
, ;
1
.
t
4
‘
v
,
/
‘
\, .
‘t
‘
*
,
i
I
----.-
b. Figure creatic
3. (a) Transverse CT scan of a 24-year-old enzyme supplementation. CT scan shows
.
C.
woman with CF with pulmonary and gastrointestinal symptoms. a small pancreas (arrows) with partial replacement of the pancreas
She was receiving panby fat tissue. (b) Trans-
verse Ti-weighted MR image (300/20) of a small pancreas (arrows) with an inhomogeneous signal intensity caused by the high sity of fat tissue and the intermediate signal intensity of residual pancreatic tissue. (c) Coronal Ti-weighted MR image (300/20) creas (arrows) shows inhomogeneous high signal intensity. The small pancreas shows focal areas of intermediate signal intensity pancreatic tissue that has not been replaced by fat tissue and larger areas of high signal intensity from fat tissue.
Figure
(a) Transverse
4.
CT scan
of
a 27-year-old
woman
with
CF
with
pulmonary
and
gastrointestinal
symptoms.
She was
signal of the from
treated
intenpanthe
with
pancreatic enzyme supplementation and received insulin for diabetes mellitus. CT scan shows complete atrophy of the pancreas (arrows), which shows normal attenuation. There are no signs of replacement of the pancreas by fat tissue. Transverse Ti- (300/20) (b) and T2- (2,000/ 100) (c) weighted MR images demonstrate an atrophic pancreas (arrows) with the same signal intensity as that of the liver.
2.6
T2 Relaxation
2.4
Times
in Control
Subjects
and
Patients
with
T2 Relaxation 00
1.S
Patients
1.6
S
1.4
.
1.2 1.0
with
0
S
Liven Normal
0
*
y
Abnormal
.
0.2 0.0
*
control sibjcu
CF vith
Significantly
(msec)
. .
Subjects
66.64±15.11 68.52
± 12.07
pancreas
All patients with CF Patients with CF with steatonrhea Patients with CF without steatorrhea
0.6 0.4
Time
Control CF
96.37±31.86k pancreas
CF
different
(P < .05) from
that
92.35 97.44 71.98 of control
± 40.72* ± 44.36 ± 2.28
... ... ...
subjects.
CF
vltit
asunr.bo.s
Figure
5. The pancreas-liver signal intensity ratio on T2-weighted MR images (2,000/ 100) in control subjects (n 27) and patients with CF with (n i4) and without (n 3) steatorrhea. Patients with diabetes mellitus who
required
insulin
are denoted
by an as-
tenisk.
sue, the signal intensity was moderate to very high (pancreas-liver ratio, 1.62-2.03; mean, 1.83) on the T2weighted
Volume
images
179
(2,000/50)
Number
#{149}
1
(Fig
ic)
but moderately high (pancreas-liver ratio, 1.29-i.80; mean, 1.55) on the T2-weighted images (2,000/ 100). In patients with partial fatty replacement of the pancreas, the T2-weighted images showed no typical pattern. The T2 relaxation times were significantly longer (P < .05) for the pancreas and liver of the patients with CF (Table). In our study, water was orally administered as a contrast medium to
delineate and bowel
the pancreas from stomach loops. In patients with fatty replacement of the pancreas, this resulted in excellent contrast on the Ti-weighted images. However, the delineation was less clear on the T2weighted images. There was complete agreement in interpretation of the MR images and CT scans by both radiologists. Theme were no false-negative findings. There was, however, one false-posi-
Radiology
185
#{149}
tive finding for a patient with CF without steatorrhea. Quantification of the agreement between the two coefficient of .95 and a Cohen K of 0.95 (standard error, 0.15). MR imaging and CT had similar sensitivities (94%) and specificities (100%). The positive predictive value was 100% and the observers
resulted
negative
in a correlation
predictive
value
was
96%
for both modalities. There was a statistically significant difference between the signal intensity ratio of pancreas and liven and between pancreas and subcutaneous fat in patients with CF and in control subjects. No difference in size of the pancreas was noted in patients with CF on in the control subjects. There was, however, indication that the pancreas was enlarged in patients with complete fatty replacement of the pancreas. Additional findings at MR imaging and CT included hepatosplenomegaly (n 4), hepatomegaly (n = 3), splenomegaly (n 1), cholelithiasis (n 1), sludge (n 1), micmogallbladden (n 2), and renal calculi (n = 1).
In this series, pancreatic involvement by CF had three appearances on MR images: (a) lobulated enlarged pancreas with complete fatty replacement corresponding to lipomatous pseudohypemtrophy (this is seen as an enlarged pancreas with high signal intensity on both Ti- and T2-weighted images) (Fig i) (10); (b) atrophied fatty pancreas with variable degrees of fibrofatty meplacement (Fig 3) (4,7) (this is seen as a small pancreas with an inhomogeneous high signal intensity on the Ti-weighted images due to the abundant amount of fat tissue scattered between atrophic pancreatic tissue); and (c) atrophied pancreas without fatty replacement (Fig 4) (only atrophy is seen on MR images, and there is no change in signal intensity on the Ti- and T2-weighted images).
A fourth pattern, described in the biterature although not present in this series, is pancreatic cystosis, which meflects cyst formation due to inspissated Pancreatic
cystosis,
which
has been reported to be suggestive of complete cystic transformation of the pancreas, shows the same morphologic appearances on CT scans and MR images as the cases that are described as Iipomatous pseudohypertrophy (10,11) (Fig i). It is suggested that it represents one end of the spectrum of the pancreatic disease in CF-true cysts that eventually
undergo
that become mality (10).
186
#{149} Radiology
depicting
fatty
liposclemotic
the predominant
changes
abnor-
infiltration
of the
pan-
creas, while the opposite is true for depicting gallbladder disease (7). The pancreas morphologic
could
be easily analyzed changes and, in this
for
study, there was good correlation with the CT findings of the pancreas with a high sensitivity (94%) and specificity (100%) for MR imaging. The main disadvantage of MR imaging was the inability to show the small calcifications in the kidneys, pancreas, and gallstones that may be found in CF (7,13). Hepatosplenomegaly with signs of portal hypertension with or without varices and a microgallbladdem were additional findings at MR imaging (14). Theme is a broad spectrum of severity of clinical and morphologic findings in pancreatic
DISCUSSION
secretions.
All patterns described are the result of precipitation of relatively insoluble proteins, which causes obstruction of the small pancreatic ducts. This precipitation is related to the low water content of the ductal fluid caused by the impaired anion transport in CF (i2). The high signal intensity of the fatty pancreas on MR images is due to the short Ti relaxation time of the protons in fat (Table). MR imaging is considered to be superior to sonography in
and
hepatic
changes
function
tests
(16).
tients
function
in
these
pa-
be normal. However, the deof pancreatic tissue in these patients may be considerable because exocnine pancreatic insufficiency occurs only when more than 98%-99% of the entire pancreas is damaged (12). In this small group of patients, MR imaging may help detect the extent of destruction and give an indication for the development of exocnine pancreatic insufficiency that is related to the prognosis of the patient. Other causes of fatty replacement with atrophy of the pancreas include main pancreatic duct obstruction, malnutrition, Schwachman syndrome, hemochmomatosis, and viral infection (17,18). Cushing syndrome and steroid therapy may cause reversible fatty infiltration of the pancreas. Rarely, multiplc nodular fatty masses may cause the pancreas to become enlarged; this is descnibed as lipomatous pseudohypemtrophy of the pancreas (10). At histologic examination, fibrofatty replacestruction
may
tests
with
can
in such
be seen
changes
are similar
experimentally
preservation
of
cases.
to those
These
produced
by ligature
of the
main
pancreatic duct (i7,i8). The fatty meplacement and atrophy in CF are probably the result of this same mechanism and
are
caused
by protein
plug
obstruc-
tion
of acinar and larger pancreatic ducts. The degree of fat replacement and atrophy could be related to the severity of expression of CF in the mdividual patients, which results in various degrees
of pancreatic
duct
obstruction.
No correlation could be established tween the severity of pulmonary pancreatic involvement. U
beand
References 1.
Fernald
2.
Lloyd-Still
3.
Abramson SJ, Baker DH, Amodio WE. Gastrointestinal manifestations fibrosis. Semin Roentgenol 1987;
4.
Fiel SB, Friedman AC, Caroline DF, Radecki PD, Faenber E, Grumbach K. Magnetic resonance imaging in young adults with cystic fibrosis. Chest 1987; 91:181-184. McHugo JM, McKeown C, Brown MT, Weller P. Shah KJ. Ultrasound findings in children with cystic fibrosis. Br J Radiol 1987; 60:137141.
view. Boston:
5.
6.
7.
GW,
Boat
Semin John
TF.
Cystic
Roentgenol JD.
1987;
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Wright,
fibrosis:
over-
22:87-96.
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1983.
Willi UV, Reddish JM, brosis: its characteristic
JB, Bendon of cystic 22:97-113.
Teele RL. appearance
Cystic fion ab-
dominal sonography. AJR 1980; 134:10051010. Gooding CA. Lallemand DP, Brasch RC, Wesbey GE. Davis B. Magnetic resonance imaging in cystic fibrosis. J Pediatn 1984; 105:384388.
8.
9.
A minor-
ity of patients with CF (iO%-i5%) have no clinical sign of exocnine pancreatic dysfunction, and results of indirect pancreatic
of the acini
islets
in pa-
tients with CF (15). Morphologic findings of the pancreas vary from atrophy and fibrosis to complete fatty replacement of the entire pancreas. Diffuse fatty replacement occurs more often in older patients and represents an endstage disease of the pancreas (16). Up to this stage, theme is no correlation between histomomphologic findings and pancreatic
ment
10.
1 1.
Van de Kamer JH, ten Bokkei Huinink H, Weyers HA. Rapid method for the determination of fat in faeces. J Biol Chem 1949; 177:347-355. Lamers CBHW, Jansen JBMJ, Hafkenscheid JCM. Jongenius CH. Evaluation of exocnine and endocrine pancreatic function in older patients with cystic fibrosis. Pancreas 1990; 5:65-69. Nakamara N, Katanda N, Sakalibara A, et al. Huge lipomatous pseudohypertrophy of the pancreas. Am J Gastroenterol 1979; 72:171174. Hernanz-Schulman M, Teele RL, PerezAtayde A. et al. Pancreatic cystosis in cystic fibrosis.
12. 13. 14.
15.
16.
Radiology
1986;
158:629-631.
Dune PR, Forstner GG. Pathophysiology of the exocnine pancreas in cystic fibrosis. J Soc Med 1989; 82(suppl 16):2-10. lannaccone G, Antonelli M. Calcification of the pancreas in cystic fibrosis. Pediatn Radiol 1980; 9:85-89. Wilson-Sharp C. Irving HC, Brown RC, Chalmers DM, Littlewood JM. Ultrasonography of the pancreas. liver, and biliary system in cystic fibrosis. Arch Dis Child 1984; 59:923926. Green OC. Endocrinological complications associated with cystic fibrosis. In: Lloyd-Still JD. ed. Textbook of cystic fibrosis. Boston: John Wright, 1983; 329-349. Daneman A, Gaskin K, Martin DJ, Cutz E. Pancreatic changes in cystic fibrosis: CT and sonographic appearances. AIR 1983; 141:653655.
17. 18.
Partel 5, Bellon EMN. Haaga J. Park CH. Fat replacement of the exocnine pancreas. AJR 1980; 135:843-845. Robbins 5;. Pathologic basis of disease. Philadelphia: Saunders. 1974; 1056-1077.
April
1991
