Yonago Acta medica 1996;39:127–134

MRI Findings in Radiation-Induced Hepatic Injuries
Yuji Suto, Takashi Kato, Kotaro Yoshida, Shuji Sugihara, Masayuki Kamba
and Yoshio Ohta
Department of Radiology, Faculty of Medicine, Tottori University, Yonago 683, JapanTo evaluate radiation-induced hepatic injuries (RIHI), magnetic resonance image (MRI)
was conducted on 12 patients,1 to 6 months after radiotherapy on regions including theliver. T1-weighted and T2-weighted image (T1WI, T2WI), and gadopentetate
dimeglumine (Gd-DTPA)-enhanced T1WI were obtained. Within 1 week, these MRI
studies were repeated after chondroitin sulphate iron colloid (CSIC) administration.
MRI findings and total irradiation doses were compared. Abnormalities were seen on
one or more types of MRI in 7 patients. The total dose of irradiation was 40 or more Gy
in these patients, and 40 or less Gy in those who showed no abnormal MR findings.
Plain T2WI of the 7 cases showing MRI abnormalities demonstrated a slightly higher
signal intensity (SI) in the irradiated areas in 2, an iso SI in 2, a slightly lower or lower
SI in 3 cases. The irradiated and nonirradiated areas were clearly demarcated on GdDTPA-enhanced T1WI in 4 cases. Following CSIC administration, the irradiated areas
became more marked in 3 cases. A clear demarcation between the 2 areas was obtainedwith double contrast MRI in the 7 cases. The present study indicates that MRI may be
a useful noninvasive means of evaluating RIHI.
Key words: contrast agent; MR imaging; radiation hepatitis

tissues commonly return to a near-normal
condition, but sometimes chronic changes develop (Reed and Cox, 1966; Tefft et al., 1970;
Lewin and Millis, 1973; Jeffery et al., 1980;
Garra et al., 1988; Yankelevitz et al., 1992).
So far, there have been only a few magnetic
resonance imaging (MRI) studies in the acutephase of RIHI, and most of them were doneusing a low-magnet apparatus (Unger et al.,
1987; Garra et al., 1988; Yankelevitz et al.,1992). Using a high magnetic apparatus, systematic clinical MRI studies have not beenreported so far.
We have already reported that the boundary
between the irradiated and nonirradiated fields
became well demarcated by double-contrast
MRI with combined use of chondroitin sulphateiron colloid (CSIC; Bultal, Dainippon Pharma-Repeated partial irradiation (more than 35–40Gy) of the liver often results in histopathological derangements although no changes arenoted in blood biochemical analyses (Ingold etal., 1965; Concannon et al., 1967; Unger et.,1987; Anderson, 1990). The main changes inthe acute phase of radiation-induced hepatic
injuries (RIHI) are venous stasis due to injury of
the sublobular hepatic veins (Reed and Cox,1966). There is massive panlobular congestion
with intramural red cell accumulation and mild
proliferative changes in the sublobular (centralvein) hepatic veins (Reed and Cox, 1966;Fellow et al., 1968; Tefft et al., 1970; Lewinand Millis, 1973; Jeffery et al., 1980; Garra etal., 1988; Yankelevitz et al., 1992). These histological manifestations persist for 1 to 5 months
after completion of radiotherapy, and thenAbbreviations: CSIC, chondroitin sulphate iron colloid; CT, computed tomography; FOV, field of view; GdDTPA, gadopentetate dimeglumine; MRI, magnetic resonance image; RIHI, radiation-induced hepatic injury;
SI, signal intensity; SE, spin echo; SPIO, superparamagnetic iron oxide; TE, echo time; TR, repetition time;
T1WI, T1-weighted image; T2WI, T2-weighted image

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Y. Suto et al.

ceutical Co., Osaka, Japan) (Kato et al., 1993;
Suto and Shimatani, 1995) as a negative MR
contrast material for the reticuloendothelial
system, and gadopentetate dimeglumine (GdDTPA, Magnevist, Nihon Schering, Osaka)(Weinmann et al., 1984; Niendorf et al., 1991)
as a positive contrast agent (Suto et al., 1996).
Nevertheless, that was a single case report.
In the present study, we carried out a retrospective investigation to evaluate RIHI by plain
MRI, and CSIC- and/or Gd-DTPA-enhanced
MRI. MRI findings, total irradiation dose, andthe period from completion of radiotherapy
until performing MRI were evaluated to investigate a possible correlation among them.

Subjects and Methods
We performed MRI in 12 patients (9 men and 3women; 35 to 78 years old, mean: 61 years)
who received radiotherapy on the thorax andabdomen, including the liver. Each patient
gave written consent to participate in the MR
study. Their underlying diseases were hepatocellular carcinoma (1 case), esophageal cancer(3 cases), lung cancer with metastases to thethoracic vertebrae (2 cases), metastatic adrenal
cancer (3 cases), malignant lymphoma (2 cases)
and colon cancer with abdominal lymphonodemetastases (1 case). The irradiation was external in all cases; the irradiation dose of 60Co or
linear acceleration was 1.5–2 Gy/time, with a
total administered dose of 30–54 Gy.
MRI was conducted 1 to 6 months after
completion of radiotherapy. MR images wereobtained on 2 separate days with a 1.5 Tesla
superconducting system using Magnetom H15or Vision (Siemens, Erlangen, Germany).
Precontrast T1-weighted images (T1WI) (TRms/TE ms/signal averaging = 600–700/22/3),
and T2-weighted images (T2WI) (1800–2000/90/2) were obtained using the spin echo (SE)sequence. Postcontrast T1WI were also obtained 10 min after intravenous injection of 0.1
mmol/kg of Gd-DTPA. The other imagingconditions were as follows: a slice thickness of8 mm, a gap of 2 mm, an FOV of 370 mm andan imaging matrix of 192 × 256 (T1WI) or 60 ×256 (T2WI). MRI was performed again within
1 week 1 h after intravenous injection of CSIC
(23.8 µmol Fe/kg) under the same conditions.
MRI findings of the irradiated area wereclassified into 5 patterns according to the signal
intensity (SI) relative to the nonirradiated areaof the liver parenchyma (higher, slightly higher,iso, slightly lower, lower). To evaluate thecontrast enhancemen of CSIC and/or GdDTPA, the pre- and post-contrast images werecompared.

Results
Abnormalities were revealed by one or moretypes of MRI in 7 patients who received a total
dose of irradiation of 40 or more Gy. Regardless of the type of MR images, no abnormalities
were observed in the remaining 5 patients who
received a total dose of irradiation of 40 or less
Gy (Table 1). In 3 of these 5 patients, the time
elapsed from the completion of radiotherapy
until MRI was 6 months.
Comparison of the irradiated with thenonirradiated regions of the liver on plain T1WIof patients with MRI abnormalities revealed alower SI in 2, a slightly lower SI in 1 and an iso
SI in 4 cases. The plain T2WI showed a slightly
higher SI in 2, an iso SI in 2, a slightly lower SIin 1, and a lower SI in 2 cases.
Gd-DTPA-enhanced T1WI showed a contrast enhancement in the irradiated regions thatwas stronger than that in the nonirradiated regions. In 2 cases (cases 4 and 7), MRI abnormalities were not detected on the plain T1WI or
T2WI, but were demonstrated on Gd-DTPAenhanced T1WI. The irradiated and nonirradiated zones appeared clealy demarcated on GdDTPA-enhanced T1W in 4 of the 7 cases. However, in the other 3 cases, the irradiated regions
became unclear (i.e., changed from being alower or a slightly lower SI to an iso SI).
After intravenous injection of CSIC, the SIof the nonirradiated regions decreased, whilethat of the irradiated regions increased compared to the precontrast images. After CSIC
administration, the irradiated areas on T1WIand T2WI became more marked in 3 cases.

128

MR findings in radiation-induced hepatic injuryTable 1. MR signal intensity of the irradiated area compared to the nonirradiated area

1Age (year)
Sex
Underlying disease
Total dose
[No. of fractions]
RT-MR (month)
T1WI
CSIC+/Gd-DTPA+CSIC–/Gd-DTPA+
CSIC–/Gd-DTPA–

260
60
M
M
HCC TH
5040[25] [20]63

MRI abnormalities
Case No.
345650M
TH50[25]
3H*

H*jj

I

I

SH*

SH* SH*jj

H*

66
F
ML
40[20]
672
F
Eso
40[20]
663
M
LN
40[20]
176
M
Adr
40[20]
646
MML
30[20]
1jj

H*I

I

I

I

I

I

SH*

I

I

I

I

I

I

I

I

I

I

Ijj

I

SLj

L

Lll

CSIC+/Gd-DTPA–

SL

SL

SH*

SH* SH*ll

SHll

I

I

I

I

I

I

CSIC+/Gd-DTPA+

H*

H*

H*

H*

H*

H*

H*

I

I

I

I

I

T2WI
CSIC–/Gd-DTPA–

SH

L

SH

I

SL

L

I

I

I

I

I

I

lllllll

H*

I

H*

SH*I

SH

I

I

I

I

I

I

CSIC+/Gd-DTPA–lI

H*j

35
F
Adr
54[27]
1l ll l

I

H*62
60
M
M
Eso Adr54
50[27] [25]
21j jj j

H*78
MEso40[20]37No MRI abnormalities
Case No.
89101112lll*Irradiated regions became more marked compared to the precontrast image: H, higher signal intensity; I,
iso-signal intensity; L, lower signal intensity; SH, slightly higher signal intensity; SL, slightly lower signalintensity.
Adr, metastatic adrenal cancer; CSIC, chondroitin sulfate iron colloid; Eso, esophageal cancer; HCC,
hepatocellular carcinoma; Gd-DTPA, gadopentetate dimeglumine; LN, abdominal lymphonode metastases;
ML, malignant lymphoma; RT-MR, the period from completion of radiotherapy until performing MR;
T1WI, T1 weighted image; T2WI, T2 weighted image; TH, thoracic vertebral metastases.

dose of 40 or more Gy, and thus, for the mostpart, our findings are in agreement with previous reports (Ingold et al., 1965; Concannon etal., 1967; Unger et al., 1987; Anderson, 1990).
The analysis of negative cases in the present
study demonstrated that the total irradiationdose was 30 Gy in 1 case, i.e., less than the dose
which reportedly induces hepatic radiation
injuries (Ingold et al.,1965; Fellow et al., 1968).
Three of the negative cases received a total doseof 40 Gy, but MRI was conducted after 6
months (cases 8, 9 and 11). On the other hand,
MRI abnormalities were detected after 3
months in 2 patients (cases 2 and 4) who also
received a total dose of 40 Gy. Therefore, theacute phase of RIHI might have improved by 6months in those 3 cases. Nevertheless, noThere was a case (case 4) of which abnormalities were not detected on the plain T1WI orT2WI, but were demonstrated on CSICenhanced MRI.
In all cases with identifiable abnormalities
on MRI, the contrast between the irradiated andnonirradiated regions became striking on thedouble-contrast MRI (using CSIC and GdDTPA) as compared to the precontrast images(Figs. 1 and 2).

Discussion
In the present study, the irradiated fields
showing MRI abnormalities coincided with thehepatic regions that received a total irradiation
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Y. Suto et al.

Fig. 1. A 78-year-old man with cancer of the abdominal esophagus treated by radiotherapy administeredthrough opposed anterior and posterior portals (case 4). N, nonirradiated area; R, irradiated area. The signal
intensity (SI) of the irradiated area is similar to that of the nonirradiated one on plain T1WI and T2WI. On
MRI after intravenous injection of chondroitin sulfate iron colloid (CSIC), the SI in the irradiated field isslightly higher than that of the nonirradiated area on T1WI (A) and T2WI (B), but the boundary between theirradiated and nonirradiated fields is not well demarcated. By double-contrast MRI using CSIC and GdDTPA (C), the boundary between the 2 fields becomes well demarcated (arrows).

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MR findings in radiation-induced hepatic injury

abnormalities were seen 1 month after receiving
a similar total dose of 40 Gy in 1 case (case 10),and the reasons of these discrepancies are unknown. Even in previous reports, the frequency
of detection of radiation hepatic injury and thedetection period after receiving similar irradiation doses varied greatly (Yankelevitz et al.,
1992; Clemente et al., 1992).
In the present study, the SI of the irradiatedarea varied widely on T2WI. Moreover, among
patients showing MRI abnormalities, there wasno relationship between the irradiation dose, or
the period from completion of radiotherapy until conduction of MRI, and the pattern of change
in SI on T2WI.
Using a low-magnet apparatus, Yankelevitz
and colleagues (1992) reported that 10 patients
received radiotherapy on the abdomen (36 Gy)
were followed for 4 weeks. In their study,
although the irradiation conditions were exactly
the same, only 3 of these 10 patients showed anabnormally higher SI in some areas on T2WI,
but they returned to normal within 60 days.
In our study, only 2 of 11 cases showed aslightly higher SI on T2WI. However, someirradiated areas showed a lower or slightly
lower SI on T2WI. Therefore, acute radiation
hepatitis was not essentially reflected by ahigher or a slightly higher SI on T2WI in allcases. The reasons of such difference infindings were not obvious because of lack of
specific histological findings. The differencesin SI of the irradiated areas on T2WI have beensuggested to result from the balance between SIreducing factors, such as the heterogenous
distribution of iron due to hemorrhage, and SI
elevating factors, such as edema (Suto et al.,1996). As the apparatus we used (1.5 Tesla) isdifferent from that used in previous MR studies
and is very sensitive to magnetic field inhomogeneity, a lower SI was probably detected when
signal reducing factors predominated.
After the administration of CSIC, the SI of
the nonirradiated hepatic parenchyma became
relatively higher compared to the precontrast
signal in the irradiated areas. We speculate thatsuch change reflects the hypofunction of thereticuloendothelial system in the irradiatedregions. Clemente and colleagues (1992) using131

an experimental animal model for RIHI and asuperparamagnetic iron oxide (SPIO) for MRI,
reported that regions of relatively higher (compared to the precontrast images) SI coincidedwith the irradiated field, reflecting hypofunction of the reticuloendothelial system. Ourpresent findings further support their results.
Furthermore, Clemente and colleagues (1992)
indicated that it is possible to detect abnormalities of the reticuloendothelial system by plain
MRI as early as 1 h after the completion ofirradiation, when edema has not yet developed.
MRI was performed minutes after completionof radiotherapy in their study, whereas in ourstudy MRI was performed months after it.
Nevertheless, in 1 case in the present study, theabnormal areas could be detected by CSICenhanced MRI but not by plain MRI. This has agreat significance because the functional diagnosis of the reticuloendothelial system, which
was not possible except by liver scintigraphy,
can now be done by using MRI with iron colloid
which also provides much more spatial resolution than scintigraphy.
Contrast enhancement with Gd-DTPA of
the irradiated fields may be attributed to theincreased capillary permeability that is associated with the hepatic disorders. Even the abnormal areas, which could not be detected withplain MRI in the present study, were enhanced,
while the irradiated areas showed a slightly
higher SI in some cases.
However, when using CSIC or Gd-DTPA
alone, the SI of the hepatic parenchyma in some
irradiated regions changed from a lower or aslightly lower SI before contrast administration
to an iso SI after administration, thus becoming
unclear. A thorough comparison of pre- andpostcontrast images helps to understand thedifferences in the functions of the reticuloendothelial system as well as the histopathological changes. On the other hand, such abnormalities may be overlooked on contrast MRI
using a single contrast agent alone.
By double-contrast MRI using both CSIC
and Gd-DTPA, the boundary between the irradiated and nonirradiated fields, which was not
obvious when only one contrast agent was used,became manifest. The superiority of double-Y. Suto et al.

Fig. 2. A 62-year-old man with cancer of the abdominal esophagus treated by radiotherapy administeredthrough an oblique portal (case 5). N, nonirradiated area; R, irradiated area. On plain T1WI (A), the SI of theirradiated area is similar to that of the nonirradiated one; but on T2WI (B), the SI of the irradiated area
becomes lower than that of the nonirradiated one. After administration of Gd-DTPA (C), the SI of theirradiated area is slightly higher than that of the nonirradiated one. After intravenous injection of chondroitin
sulfate iron colloid (CSIC), the SI of the irradiated field is slightly higher than that of the nonirradiated one on
T1WI (D). On T2WI (E), the SI of the irradiated field is similar to that of the nonirradiated area. By doublecontrast MRI using CSIC and Gd-DTPA (F), the boundary (arrows) between the irradiated and nonirradiatedfields becomes well demarcated.

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MR findings in radiation-induced hepatic injury

contrast MRI is thought to result from the additive combination of the positive contrast enhancement obtained with Gd-DTPA and thenegative contrast enhancement obtained withCSIC (Suto and Shimatani, 1995).
In the present study, clinical follow-up andhistological examination of the liver were notdone, and therefore it is not clear whether the133

negative MRI findings obtained in some cases
imply recovery from the RIHI. Therefore, further studies including histopathological examinations should be performed.
To summarize briefly, the present study
indicates that MRI may be a useful noninvasive
mean of evaluating RIHI.

Y. Suto et al.

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(Received August 20, Accepted September 18, 1996)

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