M e d i c a l P hy s i c s a n d I n f o r m a t i c s • O r i g i n a l R e s e a r c h

Amato et al.
Relationship Between Contrast Media and Organ Dose in CT

Medical Physics and Informatics

Original Research
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Can Contrast Media Increase

Organ Doses in CT Examinations?
A Clinical Study
Ernesto Amato1 OBJECTIVE. The purpose of this article is to quantify the CT radiation dose increment
Ignazio Salamone in five organs resulting from the administration of iodinated contrast medium.
Serena Naso MATERIALS AND METHODS. Forty consecutive patients who underwent both un-
Antonio Bottari enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective
Michele Gaeta study. The dose increase between CT before and after contrast agent administration was eval-
uated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a
Alfredo Blandino
previously validated method.
Amato E, Salamone I, Naso S, Bottari A, Gaeta M, RESULTS. An increase in radiation dose was noted in all organs studied. Average dose
Blandino A increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for
thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the
widest variance because of the differences in fibro-fatty involution. Finally, thyroids with
high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus,
a smaller increment in the dose.
CONCLUSION. Our study showed an increase in radiation dose in several parenchyma-
tous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase
from the change in attenuation measured in Hounsfield units. Because diagnostic protocols
require multiple acquisitions after the contrast agent administration, such a dose increase
should be considered when optimizing these protocols.

Keywords: CT, iodinated contrast media, radiation
absorbed dose
DOI:10.2214/AJR.12.8958
Received March 25, 2012; accepted after revision
June 7, 2012.
1
All authors: Section of Radiological Sciences,
Department of Biomedical Sciences and Morphologic
and Functional Imaging, University of Messina, Via
Consolare Valeria 1, Messina I-98125, Italy. Address
correspondence to E. Amato (eamato@unime.it).
Supplemental Data
Available online at www.ajronline.org.
AJR 2013; 200:1288–1293
0361–803X/13/2006–1288
© American Roentgen Ray Society
T
he quantification and reduction of
the absorbed radiation dose during
CT examinations is a key problem
when optimizing scan protocols,
especially with the development of high-res-
olution MDCT scanners and when multiple-
phase protocols are adopted, because evi-
dence of a potential hazard due to increments
in the radiation dose delivered to the popula-
tion as a result of the widespread use of CT is
increasing [1–3]. In clinical practice, the ad-
ministration of iodinated contrast medium is
widely used to improve image quality and di-
agnostic sensitivity.
The most widely recognized estimator of
the stochastic risk of radiation-induced can-
cer inherent in CT examinations is the effec-
tive dose, evaluated from dose measurements
and standardized conversion factors, which
are calculated by using anthropomorphic
phantoms. The effective dose has been found
to have a good correlation with dosimetric
quantities, such as the CT dose index and the
dose-length product [4]. Consequently, when
multiple-phase CT studies are performed, the
dose-length product and, hence, the overall
effective dose both increase in a linear fash-
ion along with the number of scans.
Radiation dose increases in iodine-charged
tissues and organs have been studied and pro-
posed as a conceptual basis for contrast-en-
hanced radiotherapy. Such a technique was
introduced many years ago, and several theo-
retic and experimental studies have been made
by means of Monte Carlo simulations, mea-
surements on phantoms, and in vitro or in vivo
experiments [5–11].
Both theoretic and phantom studies gener-
ally rely on the assumption of homogeneous
distribution of the high-Z element within the
target tissue and were aimed at determining
dose enhancement factors in various irradia-
tion geometries and regimens. Some micro-
dosimetric studies about contrast-enhanced
radiotherapy have been conducted, and, con-
cerning the x-ray energy spectrum emitted by
the tube, they found that radiation quality (mean
lineal energy) effects introduced by the con-
trast media are small compared with the dose-
enhancement effect [10]. Furthermore, some

1288 AJR:200, June 2013

 Relationship Between Contrast Media and Organ Dose in CT
investigators found an increase in the frequen-
cy of cellular abnormalities in patients who
underwent contrast-enhanced radiographic ex-
aminations, and these results were supported
by radiobiologic experiments [12–22].
Concerning the quantification of the ra-
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diation dose enhancement in organs impreg-
nated by a contrast medium in contrast-en-
hanced CT, the aforementioned CT dose
index or dose-length product evaluations do
not account for the increase in organ dose
due to the contrast agent, which accumulates
at different concentrations in the acquisition
phases [23]. Indeed, the radiation dose in-
crease in an organ or tissue is dependent on
the quantity of iodine taken up at the time
of the scan; on anatomic factors such as the
organ shape, volume, and position inside the
body; and finally, on the x-ray energy spec-
trum emitted by the tube. Although anatomic
information can be either assumed from gen-
eral models or obtained from the patient’s
CT images, the actual quantity of iodine ac-
cumulated by an organ during scanning re-
mains unknown, unless it is correlated to an
in vivo measurable quantity, such as attenua-
tion measured in Hounsfield units [24].
In a recent phantom study, we described
a method for evaluating the relationship be-
tween organ radiation dose increase and the
difference in tissue attenuation as measured
by Hounsfield units between two CT scans
obtained before and after contrast medium
administration [25]. Our method used a se-
ries of measurements of iodine solutions to
correlate iodine concentration with Houns-
field unit increment and a Monte Carlo simu-
lation of an anthropomorphic phantom with
iodinated organs to correlate iodine concen-
tration with the corresponding radiation dose
increment. Thus, for the thyroid, liver, pan-
creas, spleen, and kidneys, it was possible to
determine the relationship between the mea-
sured Hounsfield unit increase and the corre-
sponding radiation dose increment.
The aim of the present work was to quan-
tify the dose increment in CT due to the ad-
ministration of iodinated contrast medium in
the organs that accumulate the most contrast
medium by applying our simple experimental
method on a sample population undergoing
routine contrast-enhanced CT examinations.
Materials and Methods
Model
The method presented in our previous work
[25] allows the average dose increment in selected
organs due to the administration of iodinated con-
AJR:200, June 2013 1289
trast medium during CT to be calculated. Here, we
summarize the principles of the approach adopted
and the results obtained in the previous study.
We used a Monte Carlo simulation of an an-
thropomorphic neck and abdomen phantom ex-
posed to a simplified model of a CT x-ray source
to obtain a relationship between the iodine mass
accumulated by each organ during the scan and
the corresponding relative radiation dose incre-
ment (i.e., the difference between doses in the
presence and absence of contrast medium divided
by the dose in the absence of contrast medium):
∆D = aφb (1),
D I
where D is the dose, a and b are parameters that
are characteristic of each organ, resulting from the
fit of Monte Carlo data with the analytical form of
Equation 1, and the dimensionless quantity φI =
mI / (mI + mT) is the iodine mass fraction within
the uptaking tissue, where mT is the tissue mass
and mI is the iodine mass accumulated. The simu-
lative study was conducted for the thyroid, liver,
spleen, pancreas, and kidneys, and the values of
these constants are shown in Table 1.
Furthermore, we measured the relationship be-
tween the iodine concentration and the correspond-
ing increment in Hounsfield units (ΔHU) resulting
from the difference between the Hounsfield unit
value of the iodinated tissue and the Hounsfield
unit value of native tissue. For this purpose, we
performed a series of measurements on known di-
lutions of iodine contrast medium exposed to our
16-MDCT scanner (Somatom Definition, Siemens
Healthcare), operating at 120 kV. We showed that,
for a tissue with a density of ρT (g cm−3):
φI
∆HU = ρTγ (2).
1 − φI
The parameter γ(g−1 cm3) is defined as follows:
µI
γ=ρµ × 103 (3),
I H 2O
where γ is dependent on the x-ray energy spec-
trum, so that it is constant for a given CT scanner
operating at a definite kilovoltage value. Anyone
TABLE 1: Organ Constants
Constant
Organ a b
Liver 38.64 0.8294
Spleen 80.81 0.9090
Kidney 99.12 0.9162
Pancreas 136.35 0.9380
Thyroid 111.07 0.9545
Note—Constants were derived from a study by
Amato et al. [25].
who wishes to apply the proposed method for the
quantification of the iodine concentration and the
Hounsfield unit increment, can measure γ accord-
ing to the method described previously [25]. For
our scanner operating at 120 kV, we found a value
of γ = 2.89 ⋅ 104 [24].
Thus, we were able to find a relationship be-
tween the Hounsfield unit increment and the rela-
tive radiation dose increase for the organs studied:
∆D a ρ∆HU b
(4).
D ρTγ + ∆HU
Because a, b, and ρT are constant characteristic
of the tissue and γ has a constant value for a fixed
x-ray energy spectrum, Equation 4 allows the rel-
ative dose increase from the increment in Houns-
field units to be calculated.
Patients
We retrospectively considered 40 consecutive
patients who underwent both unenhanced and
contrast-enhanced thoracoabdominal CT in our
study. For each patient, the contrast-enhanced CT
examination was performed immediately after the
unenhanced CT, using the same scanning param-
eters and with the patient in the same position with
arms over the head.
All patients were studied using a 16-MDCT
scanner (Somatom Definition, Siemens Health-
care), the same as that used in our previous study
[25], operating at 120 kV in a helical mode with a
reconstruction slice thickness of 7 mm and a slice
gap of 7 mm. Iodinated contrast medium (iopro-
mide; Ultravist 300, Bayer Healthcare) containing
300 mg I/mL was administered IV at a dose of 1.5
mL/kg of patient weight, and contrast-enhanced
CT was performed during the portal phase (80
seconds after the start of contrast administration).
We calculated the Hounsfield unit increment by
drawing the same circular region of interest (ROI)
in a well-defined region of each parenchyma for
both unenhanced and contrast-enhanced CT. For
each patient, ROIs were drawn by the same radi-
ologists with 20 years of experience in CT. The
ROIs were placed in homogeneously uptaking re-
gions of tissues, avoiding lesions, vessels, fat in-
clusions, or other abnormalities.
The thyroid was sampled by drawing an ellipti-
cal-shaped ROI with an area of 4.6 mm2 in either
the right or left lobe in a section passing through
the middle part of the gland.
Two ROIs were drawn in the liver, one of 100
mm2 in the caudate lobe and the other 150 mm 2 in
segment IV in an axial plane passing through the
portal vein. According to recent literature [26], we
first considered fatty liver involution qualitative-
ly, on the basis of a visual comparison of the at-
tenuation of hepatic parenchyma and vessels and
 Amato et al.

then quantitatively when hepatic attenuation val- In the present work, we applied this method
Increase (%) ues were lower than 48 HU and when the hepat- in a clinical setting and evaluated 40 consec-
Relative
Dose

71
utive patients who underwent CT before and

11
ic attenuation index (liver attenuation divided by
spleen attenuation) was less than 0.8. after contrast medium administration. The re-
The spleen was sampled near the hilum with sults are in agreement with our previous data,
Kidneys

Increment

an ROI of 100 mm 2. The kidney was sampled by confirming an increase in organ radiation dose
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139
HU

drawing an ROI of 100 mm 2 in the equatorial re- in contrast-enhanced CT compared with un-
24
TABLE 2: Mean Basal Hounsfield Unit (HU) Values and Increment and Relative Dose Increase for Five Organs Studied in 40 Patients

gion. The pancreas was sampled in two regions: enhanced CT.

the head, with an ROI of 100 mm 2, which is a re- Among the parenchymatous tissues studied,
Basal

gion less subject to fibro-fatty involution, and the the kidneys showed the maximum among the
HU
34
3

head-tail passage with an ROI of 50 mm 2, which average dose increments (71%, resulting from
is the first region to undergo fibro-fatty involution. an attenuation increment of 139 HU). High re-
Increase (%)

Examples of the placement of ROIs are shown nal enhancement is, in fact, due to both their
Relative
Dose

high vascularization because they receive 20–

33
10

in Figures S1–S7, which can be seen in the AJR

electronic supplement to this article (available at 25% of the cardiac output [27] and the passage
www.ajronline.org). of iodine within the renal tubules. In particu-
Pancreas

Increment

Where two measurements were taken, as for lar, the level of contrast medium within renal
tubules can be up to 50–100 times higher than
HU

the liver and pancreas, the average Hounsfield unit

49
16

value was calculated and considered. Such values that in the blood because of the mechanisms of
were inserted into Equation 4 to estimate the per- tubular concentration and secretion [28].
Basal

centage dose increase in the five organs studied. The thyroid parenchyma showed the sec-
HU
36
10

ond highest average dose increment after the

Results kidneys. Our study found an average dose in-
Increase (%)

Average values and related standard devi- crement of 41%, resulting from a Hounsfield
Relative
Dose

ations are reported in Table 2, whereas indi- unit increment of 87%. It should be noted,
33
8

vidual results for all 40 patients are shown in however, that these average values were char-
Table S2, which can be seen in the AJR elec- acterized by a broad dispersion, as shown in
Spleen

tronic supplement to this article (available Figure 1A and confirmed by the SD. This was
Increment

at www.ajronline.org). Five of forty patients due to the dispersion (SD of basal Hounsfield
HU

20
71

(patients 7, 20, 21, 30, and 32) presented with unit level, 13) of Hounsfield unit values in un-
hepatic steatosis, diagnosed on the basis of enhanced CT of the thyroid tissue as well as
Basal

the criteria described in the previous section. the different degree of vascularization and io-
HU
48
4

For each patient, the mean Hounsfield unit dine uptake among the patients.
value in unenhanced CT, the Hounsfield unit We noticed that the increase in the dose for
Increase (%)

increment after contrast administration, and the thyroid depended on tissue density on un-
Relative
Dose

the relative percentage increases in the radia- enhanced CT. As shown in Figure 2, denser
19
3

tion dose absorbed for the five organs studied thyroids showed a lower increase in attenuation
are reported in Table S2. and, consequently, in the radiation dose. More-
Liver

The average dose increments were 19% over, we know from the literature that paren-
Increment

for the liver, 71% for the kidneys, 33% for the chymal gland attenuation is proportional to io-
HU

49
10

spleen and pancreas, and 41% for the thyroid. dine concentration both in the normal thyroid
Note—See also Table S2 for individual values for all 40 patients.

Histograms of the relative increase in radiation and in diffuse thyroid disease [29]. There is
Basal

dose for each organ are presented in Figure 1. also a linear correlation between iodine uptake
HU
50
11

and thyroid vascularity, as shown by adminis-

Discussion tering highly concentrated solutions of Lugol
Increase (%)

In a recent article [25], we described a iodine to patients affected by Graves disease

Relative
Dose

method for exploiting a series of measure- and by Doppler color-flow sonography [30, 31].
14
41

ments on phantoms of water solutions with This linear correlation can explain the inverse
varying iodine contents to correlate iodine correlation between native thyroid density and
Thyroid

concentrations with Hounsfield unit incre- dose increment because a thyroid with lower
Increment

ments. We also used a Monte Carlo simula- iodine concentration is more vascularized and
HU

87
31

tion of an anthropomorphic phantom with thus exhibits a higher Hounsfield unit incre-
iodinated organs to correlate iodine concen- ment during contrast-enhanced CT.
Basal

trations with the corresponding dose incre- Both the liver and spleen are richly vascu-
HU
75
13

ments, which revealed a close relationship larized; consequently, average Hounsfield unit
between the increase in Hounsfield units and increments of 49 and 71 HU, respectively, and
Value

the corresponding dose increments for the corresponding average dose increments of
Mean
SD

thyroid, liver, pancreas, spleen, and kidneys. 19% and 33%, respectively, were found.

1290 AJR:200, June 2013

 Relationship Between Contrast Media and Organ Dose in CT

Thyroid Liver
12 16

14
10
12
8
No. of Patients

No. of Patients
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10

6 8

6
4
4
2
2

0 0
0 20 40 60 80 100 0 5 10 15 20 25 30 35 40
Change in Radiation Dose (%) Change in Radiation Dose (%)
A B
Spleen Pancreas
14 12

12
10

10
8
No. of Patients

No. of Patients
8
6
6
4
4

2 2

0 0
0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60
Change in Radiation Dose (%) Change in Radiation Dose (%)
C D
Kidneys
16

14

12
No. of Patients

10

0
0 20 40 60 80 100 120
Change in Radiation Dose (%)
E

Fig. 1—Relative percentage radiation dose increase.

A–E, Histograms show relative percentage radiation dose increase for thyroid (A), liver (B), spleen (C), pancreas (D), and kidneys (E) in 40 patients. Pancreas (D) shows
highest dispersion in dose increment.

It is noteworthy that, in the liver parenchy-
ma, unlike the thyroid gland, no relationship
was found between the unenhanced attenuation
and radiation dose increment. In particular, the
five patients affected by liver steatosis did not
exhibit a dose increment different from the aver-
age value of the other patients without steatosis.
The spleen and pancreas showed the same
average dose increments (33%) but deriv-
ing from different Hounsfield unit increments
(71 and 49 HU, respectively). This was due to
the unequal speed of the increase in average
dose increment versus Hounsfield unit incre-
ment for these two parenchymatous tissues
caused by the anatomic differences in shape

AJR:200, June 2013 1291


80
60
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∆D/D (%)
40
20
0 gy distributions and ionization cluster analysis.
50 60
Fig. 2—Relative percentage radiation dose (D) increase in thyroid as function of basal Hounsfield unit value.
Line represents linear fit of data points. Denser thyroids show lower increase in attenuation and, consequently,
in radiation dose.
and location of the organs. The spleen has a
higher Hounsfield unit increment because of
its elevated vascularization and, consequent-
ly, reaches the same dose increment as the
pancreas, which receives such a dose for the
aforementioned geometric issues, even with a
lower vascularization in the portal phase.
Finally, the pancreas showed the highest
SD in dose increment of the abdominal or-
gans studied, which is clearly visible in Fig-
ure 1D. The average dose increment of 33%
of the pancreas resulted from an average
Hounsfield unit increase of 49%.
We are considering extending our study to
other potentially relevant organs, such as the
ovaries and testes, and to pediatric patients.
Furthermore, the clinical application of our
dosimetric model in circulatory phases other
than the portal phase is desirable to obtain in-
formation about the average dose increments
in arterial and delayed enhanced phases. For
example, it can be predicted that liver dose in-
crements in the arterial phase should be much
lower than in the portal phase because about
60–70% of the liver vascularization depends
on portal blood.
In conclusion, this method enables a sim-
ple evaluation of the increased radiation dose
to various organs after the administration of
a contrast agent on the basis of the change
in Hounsfield units. Because many CT proto-
cols require multiple acquisitions in different
phases after the administration of contrast
1292 AJR:200, June 2013
Amato et al.
Linear fit
∆D/D = −0.455 HU0 + 73.9
R = 0.23
2 Biol 1992; 37:439–443
70 80 90 100
HU (Thyroid)
material, this method would be useful to es-
timate the radiation dose to each organ in
each patient. These data could be useful for
creating new CT protocols that are tailored
for different clinical problems and patient
ages to obtain better diagnostic information
with a lower level of radiation exposure, thus
reducing the risks of cancer induction.
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F O R YO U R I N F O R M AT I O N
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AJR:200, June 2013 1293