Supplemental Digital Content
Table of Contents
1. Methods to evaluate hepatic steatosis
2. Scan parameters for diffusion-weighted imaging of the liver
3. Patients whose benign focal hepatic lesions were determined by lesion resolution
4. TSTC-liver-on-CT and negative-liver-on-CT patients who did not have adequate
follow-up
5. Patients with hepatic metastases that manifested as TSTC lesions
6. References for Supplemental Digital Content
1. Methods to evaluate hepatic steatosis
MRI is known to be the most accurate noninvasive method available to assess hepatic
steatosis. Since only a portion of the patients in our study cohort underwent liver MRI,
assessment of hepatic steatosis using MRI was only possible in these patients. Although it is
less straightforward than the use of MRI or unenhanced CT, several studies1-3 have shown
that hepatic steatosis can be evaluated using contrast-enhanced liver CT with moderate
accuracy. The contrast-enhanced CT method had an advantage that it could be consistently
applied to all patients of our study. One major limitation with contrast-enhanced CT, however,
is the lack of truly generalized criteria to diagnose hepatic steatosis on contrast-enhanced CT,
largely related to the variability caused by differences in contrast-enhancement methods.
Therefore, we evaluated hepatic steatosis using contrast-enhanced CT for the entire study
cohort and, in addition, using both MRI and contrast-enhanced CT in the patients who had
undergone liver MRI. Given the limited accuracy of the contrast-enhanced CT method, we
then estimated the prevalence of hepatic steatosis for the entire study cohort by referring to
the comparative results of MRI and CT obtained in the subset of patients who had undergone
MRI.
The contrast-enhanced CT assessment of hepatic steatosis was according to quantitative
attenuation measurement (in Hounsfield unit [HU]) of the liver and spleen using a standard
region of interest (ROI) technique at a commercial picture archiving and communication
system workstation (PetaVision; Asan Medical Center, Seoul, Korea). Mean liver and spleen
attenuation was obtained by averaging three 1-cm2 square ROIs placed in each organ. The
ROIs were placed in the central portion of the right hepatic lobe approximately at the level of
hepatic hilum and in the central portion of the spleen at a similar level. Special care was taken
to measure representative areas of hepatic and splenic parenchyma and to avoid any focal
lesions or visible vessels. The ROI measurement was performed for all but two patients (861
patients). Two patients could not be evaluated due to the presence of numerous hepatic cysts
and/or hamartomas and history of splenectomy. Hepatic steatosis was diagnosed on contrastenhanced CT if the mean hepatic attenuation was lower than the mean splenic attenuation by
greater than 20 HU.1, 2
The MRI assessment of hepatic steatosis used a well-established dual-echo T1-weighted
imaging method which compares hepatic signal intensity between in-phase and opposedphase T1-weighted MR images. Hepatic signal intensity was measured using a standard ROI
technique at a commercial picture archiving and communication system workstation
(PetaVision; Asan Medical Center, Seoul, Korea). Three 1-cm2 square ROIs were placed in
the central portion of the right hepatic lobe approximately at the level of hepatic hilum, with a
particular care to measure representative areas and to avoid any focal lesions or visible
vessels. The ROIs on the in-phase images were copied on to the opposed-phase images so
that the corresponding ROIs were placed in the same location. Hepatic fat fraction was
derived from the ROI measurements using the following equation: fat fraction = (Sin  Sout) 
2Sin  100 (%), where Sin is the signal intensity on the in-phase image and Sout is the signal
intensity on the opposed-phage image. Hepatic steatosis was then diagnosed on MRI when
the average hepatic fat fraction value of the three ROI locations was greater than 1.5%.4
2. Scan parameters for diffusion-weighted imaging of the liver
Diffusion-weighted images were acquired using a respiratory-triggered, single-shot echo
planar sequence with diffusion-weighted gradients (i.e., b-factors) of 0, 50, and 900 s/mm2
applied in three orthogonal directions. The other scan parameters for diffusion-weighted
imaging were as follows: TR of approximately 3000-5000 ms; TE of 81 ms; slice section
thickness of 6 mm; interslice gap of 1.2 mm; matrix of 192×162; number of signal averages
of 5; use of parallel imaging technique with an acceleration factor of 2; fat saturation using
the chemical shift-selective fat suppression technique; and rectangular field of view to fit.
3. Patients whose benign focal hepatic lesions were determined by lesion resolution
Case
number
1
Age
F
Gender
55
Post-resolution
follow-up length
29 months
Additional imaging features
Size: <1 cm
MRI: typical findings of a benign lesion*
18
F-FDG PET/CT: negative
2
M
61
18 months
Size: <1 cm
MRI: typical findings of a benign lesion*
18
F-FDG PET/CT: negative
3
F
67
12 months
Size: <1 cm
MRI: typical findings of a benign lesion*
18
F-FDG PET/CT: negative
4
F
44
23 months
Size: approximately 1.5 cm
MRI: ill-define patchy abnormal parenchymal signal
to suggest an inflammatory lesion
5
M
65
23 months
Size: approximately 1.3 cm
MRI: ill-define patchy abnormal parenchymal signal
to suggest an inflammatory lesion
18
F-FDG PET/CT: negative.
6
M
56
29 months
Size: approximately 1.2 cm
MRI: ill-define patchy abnormal parenchymal signal
to suggest an inflammatory lesion
*Bright high signal on T2-weighted imaging, lack of enhancement on contrast-enhanced T1-weighted imaging,
and lack of diffusion restriction.
4. TSTC-liver-on-CT and negative-liver-on-CT patients who did not have adequate
follow-up
Mean age (SD)
TSTC-liver-on-CT (n=31)‡
Negative-liver-on-CT (n=24)‡
65.8 years (11.0)
67.5 years (12.6)
Gender
Female
12 (39)
9 (38)
Male
19 (61)
15 (63)
Colon
20 (65)
7 (29)
Rectum
11 (35)
17 (71)
Stage 0
3 (10)
3 (13)
Stage 1
5 (16)
5 (21)
Stage 2
5 (16)
4 (17)
Stage 3
14 (45)
12 (50)
4 (13)
0 (0)
Tumor location
AJCC stage at presentation*
Stage 4
Serum CEA (ng/mL), median
(range)†
(n=28)
(n=19)
2.4 (0.51398)
2.3 (0.48148)
Data are shown as the number of patients with percentages in parentheses (sum of which may not be 100% due
to rounding), unless otherwise specified. When synchronous cancers were present, data are presented according
to the most-advanced lesion.
*According to AJCC 7th edition and excluding hepatic metastasis. Staging was classified according to
pathologic TNM whenever applicable. In those patients treated nonsurgically, clinical staging information was
used when pathologic staging data were lacking. The T and N stages of the rectal cancers that were treated using
preoperative chemoradiation were determined at the pretreatment rectal MRI.
†Number of patients with serum CEA data is provided in the parentheses.
‡Reasons for the lack of adequate follow-up included transfer to another hospital or loss on follow-up (n=25),
lack of imaging follow-up in patients who underwent curative endoscopic resection of early cancer (n=3), noncancer-related death (n=2), or unspecified reasons (n=1) in TSTC-liver-on-CT group and were transfer to
another hospital or loss on follow-up (n=17), curative endoscopic resection of early cancer (n=6), or unspecified
reasons (n=1) in negative-liver-on-CT group.
5. Patients with hepatic metastases that manifested as TSTC lesions
AJCC stage at presentation*
T
N
M
Overall
Case
number
Age
(years)
Gender
Tumor location
Serum CEA
(ng/mL)
1
56
M
Rectum
3
1
0
3B
1.2
2
54
M
Rectum
3
1
0
3B
1.7
3
61
F
Rectum
4
2
1
4B
4
79
F
Ascending colon
3
1
0
3B
1.1
5
68
M
Rectum
3
1
0
3B
3.0
53
*According to AJCC 7th edition and excluding hepatic metastasis. Staging was classified according to
pathologic TNM whenever applicable. In those patients treated nonsurgically, clinical staging information was
used when pathologic staging data were lacking. The T and N stages of the rectal cancers that were treated using
preoperative chemoradiation were determined at the pretreatment rectal MRI.
6. References for Supplemental Digital Content
1)
Kim DY, Park SH, Lee SS, et al. Contrast-enhanced computed tomography for the
diagnosis of fatty liver: prospective study with same-day biopsy used as the reference
2)
3)
4)
standard. Eur Radiol. 2010;20:359-366.
Jacobs JE, Birnbaum BA, Shapiro MA, et al. Diagnostic criteria for fatty infiltration
of the liver on contrast-enhanced helical CT. AJR Am J Roentgenol. 1998;171:659664.
Lawrence DA, Oliva IB, Israel GM. Detection of hepatic steatosis on contrastenhanced CT images: diagnostic accuracy of identification of areas of presumed focal
fatty sparing. AJR Am J Roentgenol. 2012;199:44-47.
van Werven JR, Marsman HA, Nederveen AJ, et al. Assessment of hepatic steatosis in
patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo
MR imaging, and point-resolved 1H MR spectroscopy. Radiology. 2010;256:159-168.