Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
1227
Regenerating Nodules in Hepatic Cirrhosis: MR Findings with Pathologic Correlation
Takamichi Murakami1 Chikazumi Kuroda1 Taro Marukawa1 Koushi Harada1 Kenichi Wakasa2 Masami Sakurai2 Morito Monden3 Akinori Kasahara4 Sumio Kawata5 Takahiro Kozuka1
To establish
images
clearly
the pathologic
of the cirrhotic
basis
liver, we obtained
whom partial hepatectomy patients), or autopsy (one
for hepatoma patient) was
for small
low-intensity
MR images
nodules
in 26 patients
seen
on MR
with cirrhosis
in
(15 patients), subsequently
laparoscopy for cirrhosis (10 performed. Small low-intensity with short TEs (10-13 msec) in 13 of the
nodules were seen on gradient-echo images 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition.
We conclude iron deposits
prolonged nodules. AJR
that small low-intensity in regenerating
TEs are useful
155:1227-1231,
A study published
nodules,
to confirm
December
nodules observed
on MR images are caused by
and that gradient-echo
the presence
images
of iron deposits
with short
and
in regenerating
1990
in 1987 reported
that regenerating
nodules
were sometimes
demonstrated as small low-intensity nodules on T2-weighted spin-echo or gradientecho MR images [1]. It was suggested in other previously published papers that small low-intensity nodules seen on MR images of the liver in cirrhotic patients
might Received April 1 9, 1990; accepted June28, 1990.
after revision
‘ Department of Radiology, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553, Japan. Address reprint requests to T. Murakami. 2 Department of Pathology, Osaka University
Medical 3The University 4The
Osaka
Second Medical
Department of Surgery, Osaka School, Osaka 553, Japan.
Department
University
Medical
of
Intemal
School,
Medicine,
Osaka
553,
Japan. 5The Second Osaka University Japan.
signal
loss due to the magnetic
susceptibility
effect
caused
by
clearly
the pathologic
basis
sequences spin-echo
to demonstrate and gradient-echo
Materials
and Methods
for small
low-intensity
small low-intensity techniques.
nodules
nodules.
Moreover,
also were
determined
optimal with
Osaka 553, Japan.
School,
First
represent
deposited iron in regenerating nodules [2-4]. However, direct correlations of MR and pathologic findings had not been performed. In this study, we correlated MR images of cirrhotic patients with gross and microscopic findings to establish more
Department Medical
of Internal Medicine, School, Osaka 553,
0361 -803X/90/1 556-1 227 © American Roentgen Ray Society
Between October 1988 and September 1989, 78 consecutive patients with clinically diagnosed liver cirrhosis were studied by using MR imaging to screen for liver tumors. A histologic diagnosis of liver cirrhosis was made within 3 months after MR examination in 26 of these patients at the time of partial hepatectomy for hepatoma (1 5 patients), laparoscopy
with liver biopsy (10 patients), or autopsy (one patient). We analyzed the MR and pathologic findings in these 26 patients. The cause of liver cirrhosis was alcoholism in four patients, hepatitis in 18, and unknown in four. Twenty-two of the 26 patients were men and four were women;
they were 35-69
years
old.
MURAKAMI
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
1228
MR imaging was performed with a superconducting magnet operating at 1 .5 T (Magnetom, Siemens). MR images were obtained by using spin-echo sequences with 600-850/1 5 (TR/TE) and 18002600/70 with ECG gating. Gradient-echo (fast low-angle shot imaging) sequences were performed with 1 50/1 0-1 3,1 4-25/30-90#{176} (TR/ TE/flip angle). The slice thickness was 8-1 0 mm. Two signal acquisitions were used for Ti - and T2-weighted spin-echoimages and one signal acquisition for gradient-echo images. Spin-echo images were
ET AL.
AJR:155,
December
moderate iron deposits in regenerating nodules nized histologically (Fig. 1). In the remaining
marked
iron deposits
regenerating
and fused; decrease nodules
low-intensity
nodules
as the TE was prolonged, in the signal
were
seen
intensity
images
(Fig.
13 patients
in whom
view of 33.3 cm. The gradient
moment
nulling
used
regenerating
nodules
for
images,
and
tech-
Small low-intensity nodules were seen on Ti -weighted spin-echo images in only three of the 1 3 patients with iron deposits and in none of the 1 3 patients without iron deposits. The number of low-intensity nodules seen in patients with
the
nique
T2-weighted
spin-echo
eliminating
spin-echo
nulling
flow
images.
artifacts
For
technique
was
used
gradient-echo
the
presaturation
for Ti
images,
-
the
and T2-weighted gradient
moment
used in 1 6 patients and the presaturation technique was used in 1 0 patients. The gradient-echo images were obtained with breath-holding (about 20 msec). Three radiologists evaluated the MR images of the 26 patients without knowledge of the pathologic findings, paying special attention to the detectability, variations in intensity, and size of small lowintensity
was
and
eosin
infiltration
into
liver
cells
and
specimens
and the
of the liver were
Prussian fibrous
Kupifer
cells
blue. septa
The
and
MR
images
by using
the
same
stained
degree
the
amount
in regenerating
were estimated by two pathologists. In 1 4 of the 26 patients, formalin-fixed with
deposits
of
inflammatory
of iron
nodules
and
liver specimens pulse
used for in vivo MR images. MR images specimens could not be obtained because
sequences
were
with hematoxcell
deposited fibrous
in septa
were studied that
had
been
of the remaining 12 liver of their small size.
Results Small low-intensity nodules in the liver were seen on gradient-echo images using short TEs in 1 3 of the 26 patients. In these 13 patients, slight-to-marked iron liver cells and Kupffer cells of regenerating
deposits in both nodules were
recognized by histologic examination. Low-intensity nodules appeared larger and clearer on gradient-echo images as the TE was prolonged in 12 of the 13 patients in whom slight-to-
was
no, or very were
small
shown
and
their
images
slight, by histologic
outlines
in the
iron deposits
were
in
examination.
obscure.
On T2-weighted images, small low-intensity nodules were seen in 12 of the 13 patients with iron deposits, but the number of small low-intensity nodules was smaller and their contours
nodules.
In all 26 cases, ylin
iron
on gradient-echo
2). No low-
intensity
was
seen
larger
there was an apparent
of the liver and no low-intensity
on gradient-echo
were
cells of
appeared
acquired with a 256 x 256 matrix and gradient-echo images with a 256 x 256 rectangular matrix. A body coil was used with a field of technique
nodules
were recogpatient with
in both liver cells and Kupifer
nodules,
1990
marked iron
were more obscure
used iron
(Figs.
deposits
deposits
recognized
1 and
in Kupffer
histologically,
and the signal intensity
than when gradient-echo
2). In two in liver cells
of the
cells
and
moderate
of regenerating
low-intensity
images
1 2 patients
in whom or marked
nodules
nodules
of the liver surrounding
were
were obscure,
low-intensity
nodules apparently was low on T2-weighted spin-echo images (Fig. 2). Iron deposits in the fibrous septa were seen in five patients in whom low-intensity nodules were seen only on gradientecho images, but the deposition was slight. Small low-inten-
sity nodules surrounded by high-intensity only on T2-weighted spin-echo images
septa were seen in two of the 13
patients without iron deposits. Microscopic examination of the liver revealed marked inflammatory cell infiltration into the fibrous septa in these two patients (Fig. 3). In the other 11
patients
without
cell infiltration
iron deposits, into the fibrous
mild-to-moderate septa
was
scopically.
Fig. 1.-Cirrhosis with moderate iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2400/70, shows small low-intensity nodules (arrows). B, Gradient-echo MR image with a short TE, 150/10/55#{176}, shows small low-intensity nodules clearly (arrowheads). C, Small low-intensity nodules appear larger and clearer on gradient-echo MR image as TE is prolonged, 150/23/55#{176} (arrows).
inflammatory
recognized
micro-
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
AJR:155,
December
1990
MR
OF
REGENERATING
Direct correlation of MR images of resected specimens with gross and microscopic findings revealed that small, lowintensity nodules seen on gradient-echo images were iron deposits in regenerating nodules (Fig. 4). Low-intensity nodules in the resected specimens with iron deposits in regenerating nodules appeared larger and clearer on gradient-echo images as the TE was prolonged (Fig. 4); these findings coincided with gradient-echo images obtained in vivo (Figs. 1 and 2). Small low-intensity nodules were not observed on MR images of resected specimens that did not have iron deposits in regenerating nodules. The two patients with marked inflammatory cell infiltration into the fibrous septa were not included in this direct correlation study.
NODULES
IN CIRRHOSIS
1229
Discussion Siderosis of the liver is common in patients with liver cirrhosis [5-8]. However, since iron deposits in regenerating nodules are small [6, 7] and their distribution is patchy [9], imaging techniques other than MR fail to depict the deposition of iron in the liver. In patients with cirrhosis, regenerating nodules were reported to appear as small low-intensity nodules on MR images [1]. We [2] and Ohtomo et al. [3, 4] hypothesized that the small low-intensity nodules might represent signal loss due to the magnetic susceptibility effect caused by deposited iron in regenerating nodules in the cirrhotic liver. Our direct pathologic-MR correlation in this
Fig. 2.-Cirrhosis with marked iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2000/70, shows apparent low signal intensity of liver and small low-intensity nodules (arrow), but they are somewhat obscured by respiratory motion and magnetic susceptibility caused by deposited iron. B, Gradient-echo MR image with a short TE, 150/12/300, shows small low-intensity nodules more clearly (arrowheads). C, Gradient-echo MR image with prolonged TE, 150/18/30#{176}, shows apparent decrease in signal intensity of liver and no low-intensity nodules because of enhancement of magnetic susceptibility effect.
Fig. 3.-Cirrhosis without iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2000/70, shows small low-intensity nodules surrounded B, Gradient-echo MR image, 150/12/600, does not show nodules. C, Marked inflammatory cell infiltration into fibrous septa is noted. (H and E stain)
by high-intensity
septa
(arrows).
MURAKAMI
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
1230
Fig. 4.-
Formalin-fixed
A, Regenerating B, Gradient-echo
liver specimen with iron deposits
in regenerating
ET AL.
AJR:155,
December
1990
nodules.
nodules contain iron deposits ranging from 2 to 9 mm. (Prussian MR image with a short TE, 150/10/90#{176}, shows low-intensity
blue stain) nodules (3-1 1 mm)
corresponding
to iron deposits
in regenerating
nodules. C, Low-intensity nodules (4-35 coincided with in vivo gradient-echo
mm) appear larger MR images.
and fused
(arrows)
on gradient-echo
series confirmed that the low-intensity nodules observed on gradient-echo images were iron deposits in regenerating nodules. The gradient-echo technique without a refocusing 180#{176} pulse is useful in depicting iron deposits in regenerating nodules because it is more sensitive than the spin-echo technique to the magnetic susceptibility effect caused by the presence of iron [10-14]. Small low-intensity nodules appear larger and sometimes clearer on gradient-echo images as the TE is prolonged, because the magnetic susceptibility effect is enhanced as TE is prolonged [1 0, 1 1 , 1 4]. Therefore, in general, gradient-echo images with prolonged TEs are more useful than gradient-echo images with short TEs in depicting iron deposits in regenerating nodules. However, in patients with marked iron deposits in regenerating nodules, it is difficult to demonstrate small low-intensity nodules because lowintensity nodules are fused and become unclear on gradientecho images with prolonged TEs. Therefore, gradient-echo images with short and prolonged TEs should be obtained in patients with liver cirrhosis to confirm iron deposits in regenerating nodules. In this study, we obtained gradient-echo images with vanable TEs, but we think that it is adequate and better to obtain only in-phase images with short and prolonged TEs in order to eliminate the chemical-shift effect. The T2-weighted spin-echo technique is also influenced by the magnetic susceptibility effect [15, 16]. However, low signal-to-noise ratios and contrast-to-noise ratios due to respiratory motion and the magnetic susceptibility effect caused
MR image
as TE is prolonged,
150/15/900.
These
findings
by deposited iron obscured low-intensity nodules on T2weighted spin-echo images withouth breath-holding. Therefore, T2-weighted spin-echo images are not useful in confirming iron deposits in regenerating nodules. The regenerating nodules might be shown as low-intensity
nodules
because
the fibrous
septa infiltrated
by inflammatory
cells had relatively high intensities on T2-weighted images (Maeda et al., presented at the annual meeting of the Radiological Society of North America, November 1 989). However, in this study, small low-intensity nodules surrounded by highintensity septa were seen only on T2-weighted spin-echo images in the two patients with marked inflammatory cell infiltration into the fibrous septa, but they were not seen in the remaining 1 1 patients with mild or moderate inflammatory cell infiltration into the fibrous septa. No iron deposits in
regenerating
nodules
were seen in these 13 patients.
There-
fore, our results suggest that small low-intensity nodules observed only on T2-weighted spin-echo images in cirrhotic patients without iron deposition may depend on the degree of inflammatory cell infiltration into the fibrous septa. As to the cause of the small low-intensity nodules, Ohtomo et al. [4] suggested that regenerating nodules surrounded by vascular fibrous septa might be another possible reason for the presence of small low-intensity nodules [4]. In our series, there were no cases in which regenerating nodules were
surrounded
by vascular
fibrous
septa.
On the basis of our results, we conclude that small lowintensity nodules seen on MR images are iron deposits in regenerating nodules. Gradient-echo images with short and
AJR:155,
December
MR
1990
prolonged
TEs are useful to confirm with iron deposition noninvasively.
OF
REGENERATING
regenerating
nodules
NODULES
7. Kent G, Popper H. Liver biopsy in diagnosis of hemochromatosis. Am J Med 1968;44:837-841 8. Pachet GS, French SW, Levy J, MacDonald RA. Histologic and chemical tissue iron: significance for hemochromatosis. Arch Pathol Lab Med 1965;79:452-461
ACKNOWLEDGMENT
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
We thank
Nobuhiro
1231
IN CIRRHOSIS
Satoh
for suggestions.
REFERENCES 1 . ltai Y, Ohnishi 5, Ohtomo K, et al. Regenerating nodules of liver cirrhosis: MR imaging. Radiology 1987;165:419-423 2. Murakami T, Marukawa T, Kuroda C, et al. Siderotic regenerating nodules in liver cirrhosis: evaluation by gradient echo (FLASH) imaging 1 .5T. Nippon Igaku Hoshasen Gakkai Zasshi 1989;49: 1427-1429 (in Japanese) 3. Ohtomo K, ltai Y, Ohtomo Y, Shiga J, Minami M, ho M. MRI demonstration of pseudolobules of liver cirrhosis: particular reference to iron deposits on autopsied specimens. Nippon Igaku Hoshasen Gakkai Zashi 1989;49(5): 681-683 (inJapanese) 4. Ohtomo K, Itai Y, Ohtomo Y, Shiga J, ho M. Regenerating nodule of liver cirrhosis: MR imaging with pathologic correlation. AJR 1990;154:505-507 5. Runge VM, Clanton JA, Smith FW, et al. Nuclear magnetic resonance of iron and copper disease states. AJR 1983;141 :943-948 6. Williams R, Williams H5, Scheuer PJ, Pitcher CS, Loiseau E, Sherlock S. Iron absorption and siderosis in chronic liver disease. Q J Med 1967;141 :151 -1 66
9. Searle JW, Kerr JFR, Halliday JW, Powell LW. Iron storage disease. In: MacSween RNM, Anthony PP, Scheuer PJ, eds. Pathology of liver. New York: Churchill Livingstone, 1987:181-201 1 0. Frahm J, Melboldt KD, Hanicke W. Direct
field inhomogeneities
by gradient
FLASH
MR imaging of magnetic Magn Reson Med
compensation.
1988;6:474-480 1 1 . Hendric RE, Kneeland
trast-to-noise
JB, Stark DD. Maximizing signal-to-noise ratios in FLASH imaging. Magn Reson Imaging
and con1987;5:
117-1 27 1 2. Buxton
RB, Edelman RR, Rosen BR, Wismer GL, Brady TJ. Contrast in rapid MR imaging: Ti- and T2-weighted imaging. J Comput Assist Tomogr
1987;1 1(1):7-16 13. Wendt RE III, Wilcott of susceptibility-induced
MR Ill, Nitz W, Murphy PH, Bryan RN. MR imaging magnetic field inhomogeneities. Radiology
1988;168:837-841 Haacke EM, Tkach JA, Parrish TB. Reduction ofT2 dephasing in gradient field-echo imaging. Radiology 1989;170:457-462 1 5. Edelman RR, Johnson KA, Buxton RB, et al. MR of hemorrhage: a new approach. AJNR 1986;7:751-756 16. Winkler ML, Thoeni RF, Luh N, Kaufman L, Margulis AR. Hepatic neoplasia: 14.
breath-hold MR
imaging. Radiology
1989;1 70:801-806
1227
Regenerating Nodules in Hepatic Cirrhosis: MR Findings with Pathologic Correlation
Takamichi Murakami1 Chikazumi Kuroda1 Taro Marukawa1 Koushi Harada1 Kenichi Wakasa2 Masami Sakurai2 Morito Monden3 Akinori Kasahara4 Sumio Kawata5 Takahiro Kozuka1
To establish
images
clearly
the pathologic
of the cirrhotic
basis
liver, we obtained
whom partial hepatectomy patients), or autopsy (one
for hepatoma patient) was
for small
low-intensity
MR images
nodules
in 26 patients
seen
on MR
with cirrhosis
in
(15 patients), subsequently
laparoscopy for cirrhosis (10 performed. Small low-intensity with short TEs (10-13 msec) in 13 of the
nodules were seen on gradient-echo images 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition.
We conclude iron deposits
prolonged nodules. AJR
that small low-intensity in regenerating
TEs are useful
155:1227-1231,
A study published
nodules,
to confirm
December
nodules observed
on MR images are caused by
and that gradient-echo
the presence
images
of iron deposits
with short
and
in regenerating
1990
in 1987 reported
that regenerating
nodules
were sometimes
demonstrated as small low-intensity nodules on T2-weighted spin-echo or gradientecho MR images [1]. It was suggested in other previously published papers that small low-intensity nodules seen on MR images of the liver in cirrhotic patients
might Received April 1 9, 1990; accepted June28, 1990.
after revision
‘ Department of Radiology, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553, Japan. Address reprint requests to T. Murakami. 2 Department of Pathology, Osaka University
Medical 3The University 4The
Osaka
Second Medical
Department of Surgery, Osaka School, Osaka 553, Japan.
Department
University
Medical
of
Intemal
School,
Medicine,
Osaka
553,
Japan. 5The Second Osaka University Japan.
signal
loss due to the magnetic
susceptibility
effect
caused
by
clearly
the pathologic
basis
sequences spin-echo
to demonstrate and gradient-echo
Materials
and Methods
for small
low-intensity
small low-intensity techniques.
nodules
nodules.
Moreover,
also were
determined
optimal with
Osaka 553, Japan.
School,
First
represent
deposited iron in regenerating nodules [2-4]. However, direct correlations of MR and pathologic findings had not been performed. In this study, we correlated MR images of cirrhotic patients with gross and microscopic findings to establish more
Department Medical
of Internal Medicine, School, Osaka 553,
0361 -803X/90/1 556-1 227 © American Roentgen Ray Society
Between October 1988 and September 1989, 78 consecutive patients with clinically diagnosed liver cirrhosis were studied by using MR imaging to screen for liver tumors. A histologic diagnosis of liver cirrhosis was made within 3 months after MR examination in 26 of these patients at the time of partial hepatectomy for hepatoma (1 5 patients), laparoscopy
with liver biopsy (10 patients), or autopsy (one patient). We analyzed the MR and pathologic findings in these 26 patients. The cause of liver cirrhosis was alcoholism in four patients, hepatitis in 18, and unknown in four. Twenty-two of the 26 patients were men and four were women;
they were 35-69
years
old.
MURAKAMI
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
1228
MR imaging was performed with a superconducting magnet operating at 1 .5 T (Magnetom, Siemens). MR images were obtained by using spin-echo sequences with 600-850/1 5 (TR/TE) and 18002600/70 with ECG gating. Gradient-echo (fast low-angle shot imaging) sequences were performed with 1 50/1 0-1 3,1 4-25/30-90#{176} (TR/ TE/flip angle). The slice thickness was 8-1 0 mm. Two signal acquisitions were used for Ti - and T2-weighted spin-echoimages and one signal acquisition for gradient-echo images. Spin-echo images were
ET AL.
AJR:155,
December
moderate iron deposits in regenerating nodules nized histologically (Fig. 1). In the remaining
marked
iron deposits
regenerating
and fused; decrease nodules
low-intensity
nodules
as the TE was prolonged, in the signal
were
seen
intensity
images
(Fig.
13 patients
in whom
view of 33.3 cm. The gradient
moment
nulling
used
regenerating
nodules
for
images,
and
tech-
Small low-intensity nodules were seen on Ti -weighted spin-echo images in only three of the 1 3 patients with iron deposits and in none of the 1 3 patients without iron deposits. The number of low-intensity nodules seen in patients with
the
nique
T2-weighted
spin-echo
eliminating
spin-echo
nulling
flow
images.
artifacts
For
technique
was
used
gradient-echo
the
presaturation
for Ti
images,
-
the
and T2-weighted gradient
moment
used in 1 6 patients and the presaturation technique was used in 1 0 patients. The gradient-echo images were obtained with breath-holding (about 20 msec). Three radiologists evaluated the MR images of the 26 patients without knowledge of the pathologic findings, paying special attention to the detectability, variations in intensity, and size of small lowintensity
was
and
eosin
infiltration
into
liver
cells
and
specimens
and the
of the liver were
Prussian fibrous
Kupifer
cells
blue. septa
The
and
MR
images
by using
the
same
stained
degree
the
amount
in regenerating
were estimated by two pathologists. In 1 4 of the 26 patients, formalin-fixed with
deposits
of
inflammatory
of iron
nodules
and
liver specimens pulse
used for in vivo MR images. MR images specimens could not be obtained because
sequences
were
with hematoxcell
deposited fibrous
in septa
were studied that
had
been
of the remaining 12 liver of their small size.
Results Small low-intensity nodules in the liver were seen on gradient-echo images using short TEs in 1 3 of the 26 patients. In these 13 patients, slight-to-marked iron liver cells and Kupffer cells of regenerating
deposits in both nodules were
recognized by histologic examination. Low-intensity nodules appeared larger and clearer on gradient-echo images as the TE was prolonged in 12 of the 13 patients in whom slight-to-
was
no, or very were
small
shown
and
their
images
slight, by histologic
outlines
in the
iron deposits
were
in
examination.
obscure.
On T2-weighted images, small low-intensity nodules were seen in 12 of the 13 patients with iron deposits, but the number of small low-intensity nodules was smaller and their contours
nodules.
In all 26 cases, ylin
iron
on gradient-echo
2). No low-
intensity
was
seen
larger
there was an apparent
of the liver and no low-intensity
on gradient-echo
were
cells of
appeared
acquired with a 256 x 256 matrix and gradient-echo images with a 256 x 256 rectangular matrix. A body coil was used with a field of technique
nodules
were recogpatient with
in both liver cells and Kupifer
nodules,
1990
marked iron
were more obscure
used iron
(Figs.
deposits
deposits
recognized
1 and
in Kupffer
histologically,
and the signal intensity
than when gradient-echo
2). In two in liver cells
of the
cells
and
moderate
of regenerating
low-intensity
images
1 2 patients
in whom or marked
nodules
nodules
of the liver surrounding
were
were obscure,
low-intensity
nodules apparently was low on T2-weighted spin-echo images (Fig. 2). Iron deposits in the fibrous septa were seen in five patients in whom low-intensity nodules were seen only on gradientecho images, but the deposition was slight. Small low-inten-
sity nodules surrounded by high-intensity only on T2-weighted spin-echo images
septa were seen in two of the 13
patients without iron deposits. Microscopic examination of the liver revealed marked inflammatory cell infiltration into the fibrous septa in these two patients (Fig. 3). In the other 11
patients
without
cell infiltration
iron deposits, into the fibrous
mild-to-moderate septa
was
scopically.
Fig. 1.-Cirrhosis with moderate iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2400/70, shows small low-intensity nodules (arrows). B, Gradient-echo MR image with a short TE, 150/10/55#{176}, shows small low-intensity nodules clearly (arrowheads). C, Small low-intensity nodules appear larger and clearer on gradient-echo MR image as TE is prolonged, 150/23/55#{176} (arrows).
inflammatory
recognized
micro-
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
AJR:155,
December
1990
MR
OF
REGENERATING
Direct correlation of MR images of resected specimens with gross and microscopic findings revealed that small, lowintensity nodules seen on gradient-echo images were iron deposits in regenerating nodules (Fig. 4). Low-intensity nodules in the resected specimens with iron deposits in regenerating nodules appeared larger and clearer on gradient-echo images as the TE was prolonged (Fig. 4); these findings coincided with gradient-echo images obtained in vivo (Figs. 1 and 2). Small low-intensity nodules were not observed on MR images of resected specimens that did not have iron deposits in regenerating nodules. The two patients with marked inflammatory cell infiltration into the fibrous septa were not included in this direct correlation study.
NODULES
IN CIRRHOSIS
1229
Discussion Siderosis of the liver is common in patients with liver cirrhosis [5-8]. However, since iron deposits in regenerating nodules are small [6, 7] and their distribution is patchy [9], imaging techniques other than MR fail to depict the deposition of iron in the liver. In patients with cirrhosis, regenerating nodules were reported to appear as small low-intensity nodules on MR images [1]. We [2] and Ohtomo et al. [3, 4] hypothesized that the small low-intensity nodules might represent signal loss due to the magnetic susceptibility effect caused by deposited iron in regenerating nodules in the cirrhotic liver. Our direct pathologic-MR correlation in this
Fig. 2.-Cirrhosis with marked iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2000/70, shows apparent low signal intensity of liver and small low-intensity nodules (arrow), but they are somewhat obscured by respiratory motion and magnetic susceptibility caused by deposited iron. B, Gradient-echo MR image with a short TE, 150/12/300, shows small low-intensity nodules more clearly (arrowheads). C, Gradient-echo MR image with prolonged TE, 150/18/30#{176}, shows apparent decrease in signal intensity of liver and no low-intensity nodules because of enhancement of magnetic susceptibility effect.
Fig. 3.-Cirrhosis without iron deposition in regenerating nodules. A, T2-weighted spin-echo MR image, 2000/70, shows small low-intensity nodules surrounded B, Gradient-echo MR image, 150/12/600, does not show nodules. C, Marked inflammatory cell infiltration into fibrous septa is noted. (H and E stain)
by high-intensity
septa
(arrows).
MURAKAMI
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
1230
Fig. 4.-
Formalin-fixed
A, Regenerating B, Gradient-echo
liver specimen with iron deposits
in regenerating
ET AL.
AJR:155,
December
1990
nodules.
nodules contain iron deposits ranging from 2 to 9 mm. (Prussian MR image with a short TE, 150/10/90#{176}, shows low-intensity
blue stain) nodules (3-1 1 mm)
corresponding
to iron deposits
in regenerating
nodules. C, Low-intensity nodules (4-35 coincided with in vivo gradient-echo
mm) appear larger MR images.
and fused
(arrows)
on gradient-echo
series confirmed that the low-intensity nodules observed on gradient-echo images were iron deposits in regenerating nodules. The gradient-echo technique without a refocusing 180#{176} pulse is useful in depicting iron deposits in regenerating nodules because it is more sensitive than the spin-echo technique to the magnetic susceptibility effect caused by the presence of iron [10-14]. Small low-intensity nodules appear larger and sometimes clearer on gradient-echo images as the TE is prolonged, because the magnetic susceptibility effect is enhanced as TE is prolonged [1 0, 1 1 , 1 4]. Therefore, in general, gradient-echo images with prolonged TEs are more useful than gradient-echo images with short TEs in depicting iron deposits in regenerating nodules. However, in patients with marked iron deposits in regenerating nodules, it is difficult to demonstrate small low-intensity nodules because lowintensity nodules are fused and become unclear on gradientecho images with prolonged TEs. Therefore, gradient-echo images with short and prolonged TEs should be obtained in patients with liver cirrhosis to confirm iron deposits in regenerating nodules. In this study, we obtained gradient-echo images with vanable TEs, but we think that it is adequate and better to obtain only in-phase images with short and prolonged TEs in order to eliminate the chemical-shift effect. The T2-weighted spin-echo technique is also influenced by the magnetic susceptibility effect [15, 16]. However, low signal-to-noise ratios and contrast-to-noise ratios due to respiratory motion and the magnetic susceptibility effect caused
MR image
as TE is prolonged,
150/15/900.
These
findings
by deposited iron obscured low-intensity nodules on T2weighted spin-echo images withouth breath-holding. Therefore, T2-weighted spin-echo images are not useful in confirming iron deposits in regenerating nodules. The regenerating nodules might be shown as low-intensity
nodules
because
the fibrous
septa infiltrated
by inflammatory
cells had relatively high intensities on T2-weighted images (Maeda et al., presented at the annual meeting of the Radiological Society of North America, November 1 989). However, in this study, small low-intensity nodules surrounded by highintensity septa were seen only on T2-weighted spin-echo images in the two patients with marked inflammatory cell infiltration into the fibrous septa, but they were not seen in the remaining 1 1 patients with mild or moderate inflammatory cell infiltration into the fibrous septa. No iron deposits in
regenerating
nodules
were seen in these 13 patients.
There-
fore, our results suggest that small low-intensity nodules observed only on T2-weighted spin-echo images in cirrhotic patients without iron deposition may depend on the degree of inflammatory cell infiltration into the fibrous septa. As to the cause of the small low-intensity nodules, Ohtomo et al. [4] suggested that regenerating nodules surrounded by vascular fibrous septa might be another possible reason for the presence of small low-intensity nodules [4]. In our series, there were no cases in which regenerating nodules were
surrounded
by vascular
fibrous
septa.
On the basis of our results, we conclude that small lowintensity nodules seen on MR images are iron deposits in regenerating nodules. Gradient-echo images with short and
AJR:155,
December
MR
1990
prolonged
TEs are useful to confirm with iron deposition noninvasively.
OF
REGENERATING
regenerating
nodules
NODULES
7. Kent G, Popper H. Liver biopsy in diagnosis of hemochromatosis. Am J Med 1968;44:837-841 8. Pachet GS, French SW, Levy J, MacDonald RA. Histologic and chemical tissue iron: significance for hemochromatosis. Arch Pathol Lab Med 1965;79:452-461
ACKNOWLEDGMENT
Downloaded from www.ajronline.org by 221.174.25.43 on 11/05/15 from IP address 221.174.25.43. Copyright ARRS. For personal use only; all rights reserved
We thank
Nobuhiro
1231
IN CIRRHOSIS
Satoh
for suggestions.
REFERENCES 1 . ltai Y, Ohnishi 5, Ohtomo K, et al. Regenerating nodules of liver cirrhosis: MR imaging. Radiology 1987;165:419-423 2. Murakami T, Marukawa T, Kuroda C, et al. Siderotic regenerating nodules in liver cirrhosis: evaluation by gradient echo (FLASH) imaging 1 .5T. Nippon Igaku Hoshasen Gakkai Zasshi 1989;49: 1427-1429 (in Japanese) 3. Ohtomo K, ltai Y, Ohtomo Y, Shiga J, Minami M, ho M. MRI demonstration of pseudolobules of liver cirrhosis: particular reference to iron deposits on autopsied specimens. Nippon Igaku Hoshasen Gakkai Zashi 1989;49(5): 681-683 (inJapanese) 4. Ohtomo K, Itai Y, Ohtomo Y, Shiga J, ho M. Regenerating nodule of liver cirrhosis: MR imaging with pathologic correlation. AJR 1990;154:505-507 5. Runge VM, Clanton JA, Smith FW, et al. Nuclear magnetic resonance of iron and copper disease states. AJR 1983;141 :943-948 6. Williams R, Williams H5, Scheuer PJ, Pitcher CS, Loiseau E, Sherlock S. Iron absorption and siderosis in chronic liver disease. Q J Med 1967;141 :151 -1 66
9. Searle JW, Kerr JFR, Halliday JW, Powell LW. Iron storage disease. In: MacSween RNM, Anthony PP, Scheuer PJ, eds. Pathology of liver. New York: Churchill Livingstone, 1987:181-201 1 0. Frahm J, Melboldt KD, Hanicke W. Direct
field inhomogeneities
by gradient
FLASH
MR imaging of magnetic Magn Reson Med
compensation.
1988;6:474-480 1 1 . Hendric RE, Kneeland
trast-to-noise
JB, Stark DD. Maximizing signal-to-noise ratios in FLASH imaging. Magn Reson Imaging
and con1987;5:
117-1 27 1 2. Buxton
RB, Edelman RR, Rosen BR, Wismer GL, Brady TJ. Contrast in rapid MR imaging: Ti- and T2-weighted imaging. J Comput Assist Tomogr
1987;1 1(1):7-16 13. Wendt RE III, Wilcott of susceptibility-induced
MR Ill, Nitz W, Murphy PH, Bryan RN. MR imaging magnetic field inhomogeneities. Radiology
1988;168:837-841 Haacke EM, Tkach JA, Parrish TB. Reduction ofT2 dephasing in gradient field-echo imaging. Radiology 1989;170:457-462 1 5. Edelman RR, Johnson KA, Buxton RB, et al. MR of hemorrhage: a new approach. AJNR 1986;7:751-756 16. Winkler ML, Thoeni RF, Luh N, Kaufman L, Margulis AR. Hepatic neoplasia: 14.
breath-hold MR
imaging. Radiology
1989;1 70:801-806
