Eur Radiol (2010) 20: 1321–1330

DOI 10.1007/s00330-009-1691-0 CHEST

Mattias Kristiansson
Fredrik Holmquist
Ultralow contrast medium doses at CT
Ulf Nyman to diagnose pulmonary embolism in patients
with moderate to severe renal impairment:
a feasibility study

Received: 26 June 2009

Revised: 21 October 2009
Accepted: 22 October 2009
Published online: 24 December 2009
# European Society of Radiology 2009
Ulf Nyman was part of an expert group of
The Swedish Council on Technology
Assessment of Health Care and The
National Board of Health and Welfare
establishing evidenced-based national
guidelines regarding diagnosis of pulmonary
embolism.
M. Kristiansson . U. Nyman (*)
Department of Diagnostic Radiology,
Lasarettet Trelleborg,
University of Lund,
231 85,Trelleborg, Sweden
e-mail: ulf.nyman@skane.se
Tel.: +46-76-8871133
Fax: +46-410-15983
F. Holmquist
Department of Diagnostic Radiology,
Malmö University Hospital,
University of Lund,
205 02,Malmö, Sweden
Abstract Objectives: To analyse
80-kVp 16-MDCT in patients with
clinically suspected pulmonary em-
bolism (PE) and diminished renal
function after a reduction in dose of
contrast medium (CM) from 200 to
150 mg I/kg. Methods: Fifty pa-
tients with suspected PE and glom-
erular filtration rate (GFR) less than
50 mL/min underwent 80-kVp
16-MDCT with 150 mg I/kg. Mean
density/image noise (1 standard de-
viation) was measured in a region of
interest in the left pulmonary artery
(LPA) and a lower lobe segmental
artery (LLSA), and the contrast-to-
noise ratio (CNR) was calculated.
The values of LPA and LLSA were
averaged. Results: Median values/
2.5–97.5 percentiles were: age
84/67–96 years, weight 65/43–
84 kg, GFR 36/21–45 mL/min, CM
dose 9.6/6.4–12 g of iodine, PA
density 353/164–495 HU and CNR
11/4.4–20. PE incidence was 16%,
and 8% and 12% of the examina-
tions were regarded suboptimal by
observer 1 and 2, respectively.
Density/CNR values were within
ranges reported for common
120-kVp MDCT protocols. None
of 32 patients with plasma-creatinine
follow-up within 1 week
experienced a rise of more than
44.2 μmol/L and none of 50 patients
had oliguria/anuria or dialysis. None
of 40 patients with a negative CT/no
anticoagulation had thromboembo-
lism during follow-up.
Conclusion: 80-kVp MDCT com-
bined with individualised ultralow CM
doses may provide satisfactory diag-
nostic quality, which should be to the
benefit of patients at risk of contrast
medium-induced nephropathy.
Keywords Computed tomography .
Contrast material . Contrast medium-
induced nephropathy .
Nephrotoxicity . Pulmonary embolism

Introduction function and diabetes mellitus, i.e. a number of CIN risk

During the past decade, the contribution of computed
tomography pulmonary arteriography (CTPA) in the
diagnosis of acute pulmonary embolism (PE) has drama-
tically increased as a consequence of major advances in CT
technology [1]. A major drawback of CTPA is the risk of
contrast medium-induced nephropathy (CIN). PE is a
common differential diagnosis in our elderly population
with a number of risk factors such as congestive heart
failure and/or chronic obstructive lung disease with
hypoxia, and is often combined with decreased renal
factors [2]. In the PIOPED II study 18.5% of the patients
with suspected PE were excluded because of elevated
serum creatinine. The situation is complicated by the fact
that scintigraphy may frequently be inconclusive [3, 4],
unavailable outside working hours and is lacking in many
smaller hospitals like ours.
In a survey of 16-channel multidetector CT (16-MDCT)
protocols for PE, CM doses ranged from 28 to 55 g of iodine
(I) [5]. Decreasing x-ray tube peak kilovoltage (kVp) from
commonly used 120 and 140 kVp [5] to 80–90 kVp brings
the x-ray spectra closer to the k-edge of the iodine and
1322
increases the iodine attenuation of photons [6–8]. This would
permit a reduction of the CM dose while keeping vascular
enhancement at the same level as that obtained at 120 and
140 kVp. At the same time modern CT technology with
increased capacity of the x-ray tubes now permits imaging at
80–90 kVp, while increasing the x-ray tube loading (tube
current–time product, i.e. milliampere seconds = mAs) to
compensate for the increased noise with decreasing tube
voltage. Thus, the diagnostic quality in terms of contrast-to-
noise ratio (CNR) may be maintained.
In a recent CTPA study in azotaemic patients [9], it was
possible to maintain pulmonary artery (PA) density at the
same level as that of 120 kVp when the CM dose was
decreased by a factor 1.6. This factor corresponds to the
density difference of iodine between 80 and 120 kVp [8, 10,
11]. Median noise and CNR was about the same at 80 and
120 kVp, though this required an almost four-fold increase in
reference effective mAs (mAseff), i.e. from 100 mAseff at
120 kVp to 380 mAseff at 80 kVp. This is to compensate for
the roughly four-fold decrease in radiation intensity to the
detectors [(120/80)3.5] that occurs when decreasing the x-ray
tube potential from 120 to 80 kVp [12]. By combining the
80-kVp 16-MDCT protocol with a CM dose tailored to body
weight (200 mg I/kg), a fixed injection time (15 s), automatic
bolus tracking and saline chaser, the median CM dose used
was only 13 g of iodine
The primary aim of the present investigation was to
report on image quality from a 1-year quality register in
using 16-MDCT in patients with clinically suspected PE and
an estimated glomerular filtration rate (eGFR) less than
50 mL/min after a further 25% CM dose reduction from 200
to 150 mg I/kg. CM dose rate was kept roughly unchanged
(≈13 mg I/kg/s) by shortening the injection time from 15 to
12 s. A secondary aim was to analyse possible events of CIN
in patients who had a post-procedural plasma creatinine.
Materials and methods
Patients referred for CTPA with a clinical suspicion of
acute PE are scheduled to be examined with an 80-kVp
16-MDCT (Siemens Somatom Sensation 16, Siemens
Medical Solutions, Forchheim, Germany) protocol if eGFR
is less than 50 mL/min, i.e. moderate (30–59 mL/min) to
severe renal impairment (15–29 mL/min) [13]. A 120-kVp
protocol is used if eGFR is 50 mL/min or more. eGFR
were calculated using the Cockcroft–Gault formula:
[1.23×(140−age in years)×adjusted body weight in kg/
plasma creatinine in μmol/L]×0.85 (if female) [14]. No
specific CIN-prophylactic regimens were instituted apart
from encouraging outpatients to drink abundantly during
12 h post-procedure or recommending the ward to ensure
adequate hydration of inpatients both before and after the
examination.
During a 1-year period (November 2007 to October 2008)
58 consecutive patients were examined with an 80-kVp
protocol with the intention to use a CM dose of 150 mg I/kg.
According to the preference of the referring physician
another 12 patients (median age 85 years) with a clinical
suspicion of acute PE and a median plasma creatinine of 144
(range 104–233) did not undergo CTPA, but were referred to
the regional university hospital for ventilation/perfusion
scintigraphy during the same period.
The results of the 80-kVp cohort were retrospectively
analysed and compared with those of an earlier published
cohort of 89 azotaemic patients also examined at 80 kVp with
the same CT equipment but using 200 mg I/kg (April 2004 to
March 2006) [9], henceforth named the reference cohort.
Only first-time examinations during the defined periods were
used for analysis. Because this was a register study as part of
the hospital’s quality assurance programme no informed
consent was needed and ethical approval for publication of
the results was waived by the local ethics committee.
Our routines include double reading of all CTPA examina-
tions, with the second reader always being a board certified
radiologist, before the final report is issued. The hospital’s
digital clinical, radiological information (RIS) and imaging
systems (PACS) were reviewed for pertinent patient data and
image analysis. Data collected at the initial examination
included age, body weight and height, baseline plasma
creatinine, eGFR, CM injection and exposure parameters, and
radiation dose presented by the CT equipment.
Computed tomography parameters
CM injection and exposure parameters are summarised in
Table 1. In both the present and the reference cohort,
imaging was performed in a cranio-caudal direction from
2 cm above the aortic arch to the inferior aspect of the heart
after asking the patient to suspend respiration without
taking a deep breath.
In the present cohort (150 mg I/kg) automatic exposure
control in the x,y plane (Care Dose, Siemens Medical
Solutions, Forchheim, Germany) was used, but was not
available for the reference cohort (200 mg I/kg). Instead
reference x-ray tube loading was based on a patient with an
88-cm circumference [15]. The individual tube loading was
calculated with the help of a computer program (http://
www.arwen.se/radiologi/omnimas) following measurement
of the widest thoracic circumference with a tape measure. A
half-value thickness (HVT) of 9 cm was chosen, i.e. the
change in object diameter that doubled or halved the mAs
setting [15].
In both cohorts a pitch of 0.5 had to be used to reach
380 mAseff at 80 kVp (maximum tube current 190 mA)
with the present CT equipment in order to keep image noise
at the same level as that of our 120-kVp protocol with 100
reference mAseff in patients with eGFR of 50 mL/min or
more. The bolus tracking used 75 mAs at 80 kVp.
CM injections (iodixanol 320 mg I/mL; Visipaque,
GE Healthcare) were performed with a power injector
 1323

Table 1 Contrast medium injection and exposure parameters used in the present and the reference cohorts [9]
Parameters Present cohort Reference cohort

Contrast medium dose (mg I/kg; maximum dose weight 80 kg) 150 200
Injection duration (s) 12 15
Injected dose rate (mg I/kg/s) 12.5 13.3
Saline chaser (mL) 50 50
Automatic bolus tracking threshold (HU) 100 100
Imaging start delay (s) 4 5
X-ray tube potential (kVp) 80 80
Reference effective x-ray tube loading (mAs) 350 380
Pitch/rotation time (s) 0.5/0.5 0.5/0.5
Collimation (mm) 16×1.5 16×1.5
Convolution kernel B40f B40f
Matrix 5122 5122
Reconstructed slice thickness/increment (mm) 3/2 3/2
HU Hounsfield units, kVp peak kilovoltage, mAs milliampere seconds

(Injektron C2, Medtron, Saarbrücken, Germany) through
an 18–20 gauge cannula placed in an antecubital vein,
preferably on the right side. The individual CM volume
and injection rate were calculated based on body weight,
CM dose/kg and CM concentration, and using a dedicated
computer program developed for calculating eGFR and CM
injection parameters from various CT protocols (OmniVis,
distributed by GE Healthcare in Nordic countries):
In each patient the density of the LPA and LLSA as well as
the image noise were averaged. Based on these average
values and assuming a maximum value of 70 HU for a fresh
clot [16, 17], CNR was calculated as (arterial density −70)/
image noise.
Subjective image quality

Image quality was subjectively evaluated independently by

CM volume ðmLÞ ¼ Weight ðkgÞ
 dose per kg ð150 mg I=kgÞ=
concentration ð320 mg I=mLÞ
Injection rate ðmL=secondÞ ¼ CM volume ðmLÞ=
injection time ð12 secondsÞ
Vascular density and image noise
Mean vascular density and image noise (1 standard deviation
of the mean density) was measured in a region of interest
(ROI) in the left pulmonary artery (LPA; Fig. 1a) and in a
lower lobe segmental artery (LLSA; Fig. 1b) on 3-mm-thick
axial images on a PACS workstation (IDS5, Sectra Imtec
AB, Linköping, Sweden). An ROI of 10–15 mm in diameter
(≈350–700 pixels) was used in the LPA. In the LLSA the ROI
was adapted to the size of the artery, usually about 3 mm
(≈30 pixels). Care was taken to avoid any partial volume
effect. The LLSA were often too narrow to obtain reliable
image noise data. Therefore, noise was measured both in the
LLSA and descending aorta at the same level and the lowest
value was registered.
two radiologists (both with 30 years’ CT experience of
thoracic imaging including 13 years’ in diagnosing PE with
CT) on a PACS workstation (IDS5, Sectra Imtec AB,
Linköping, Sweden). It was classified as excellent,
adequate, suboptimal or non-diagnostic based on vascular
density, image noise, artefacts and underlying disease such
as extensive pulmonary abnormalities or pleural effusions.
Excellent was defined as dense opacification of all
pulmonary arteries including the subsegmental without
visible noise or artefacts at a window level of 100 HU and
width of 400 HU; adequate when noise and/or artefacts
were visible in the vessels but the opacification was dense
enough to allow good depiction of all pulmonary arteries
including the subsegmental; suboptimal when vascular
density, image noise, artefacts and/or underlying disease
did not allow proper evaluation of the subsegmental
arteries; non-diagnostic when segmental or more central
pulmonary arteries could not be evaluated.
Radiation dose
Volume computed tomography dose index (CTDIvol) and
dose–length product (DLP) presented by the CT equipment
1324
Fig. 1 a Eighty-peak kilovoltage computed tomography pulmonary
angiogram in an 87-year-old female patient with an eGFR of 45 mL/
min (moderate renal impairment) and weighing 67 kg, resulting in
the following injection parameters based on 150 mg I/kg and 12-s
injection duration (12.5 mg I/kg/s): 31 mL of 320 mg I/mL (10 g
iodine) injected at 2.6 mL/s. Left pulmonary artery density 560 HU
(“Medel” = mean) and image noise 37 HU (“Std.avv” = 1 standard
deviation) and pulmonary emboli measuring 60 HU, resulting in a
contrast-to-noise ratio of 14 [(560−60)/37]. Note only faint
enhancement of the aorta. b Eighty-peak kilovoltage computed
tomography pulmonary angiogram in an 87-year-old female patient
with an eGFR of 21 mL/min (severe renal impairment) and
weighing 43 kg, resulting in the following injection parameters
based on 150 mg I/kg and 12-s injection duration (12.5 mg I/kg/s):
20 mL of 320 mg I/mL (6.4 g of iodine) injected at 1.7 mL/s. Left
lower lobe segmental artery density 395 HU (“Medel” = mean) and
image noise 21 HU (“Std.avv” = 1 standard deviation), and a left
lower lobe subsegmental artery emboli (arrow) measuring 34 HU,
resulting in a contrast-to-noise ratio of 17 [(395-34)/21]. Note
minimal enhancement of the aorta (density 83 HU)
(software version VB28B SP2, Siemens Medical Solu-
tions, Forchheim, Germany) were registered including the
DLP during bolus tracking. The effective dose per unit
DLP (ED/DLP) conversion factor reported for 120-kVp
chest examinations with the present equipment is
0.017 mSv mGy−1 cm−1 [18]. At 80 kVp a ED/DLP of
0.015 mSv mGy−1 cm−1 was used as the ED/DLP
conversion factor increases by 4.2% for each 10-kVp
increase in x-ray tube potential [18].
Follow-up
Patients’ medical charts, death certificates, anticoagulation
register, and the regional digital radiological request
(including nuclear medicine) and chemical laboratory
systems including two nearby university hospitals were
reviewed. Post-procedural plasma creatinine and any
incidence of severe CIN (oliguria/anuria or requiring
dialysis) were noted as well as any diagnosed episode of
venous thromboembolism (VTE) in patients with a nega-
tive CTPA and no anticoagulation during a follow-up
period of 3 months. CIN was defined as a plasma creatinine
rise more than 44.2 µmol/L from baseline [2] within
1 week after CTPA in the absence of an alternative
aetiology.
Statistical analysis
Statistical analyses were conducted in StatXact-6 version
6.2.0 (Cytel Software Corp., Cambridge, Mass, USA).
Mann–Whitney U test was used to analyse any difference
in subjective image quality between the present and
reference cohorts. We considered p less than 0.05 as
statistically significant. Cohen’s kappa values were calcu-
lated as a measure of agreement of subjective image quality
between observer 1 and 2 in the present cohort [19].
Strength of agreement was regarded as poor with kappa
values of 0.20 or lower, fair 0.21–0.40, moderate 0.41–
0.60, good 0.61–0.80 and very good 0.81–1.00.
Results
Eight patients in the present cohort were excluded because
of eGFR of 50 mL/min or more (n=4), because data
regarding weight and eGFR were lacking (n=1), because
of CM extravasation (n=1), because the patient was unable
to undergo the examination due to failure to cooperate (n=
1) and because of too high a CM dose (190 mg I/mL, n=1).
Thus 50 patients were left for the final analysis. Thirteen
patients were not able to elevate any arm above their heads
during acquisition.
Basic patient characteristics are presented in Table 2 and
results in terms of CM doses, vascular density, image noise,
CNR, subjective image quality, imaging time/length and
radiation doses are summarised in Table 3 including the
reference cohort. Correlation between body weight and PA
density and between body weight and CNR in the present
cohort is illustrated in Fig. 2. Image noise tended to
increase with body weight (R2 =0.131; not illustrated).
 1325

Table 2 Pre-procedural basic characteristics of the present (150 mg I/kg) and the reference (200 mg I/kg) cohorts [9] undergoing 80-kVp
16-channel multidetector computed tomography to diagnose acute pulmonary embolism
Parameters 150 mg I/kg (n=50; 39 females, 78%) 200 mg I/kg (n=89; 63 females, 71%)
Mean value Median value (2.5 and 97.5 percentiles) Mean value Median value (2.5 and 97.5 percentiles)

Age 83 84 (67–96) 82 84 (58–95)

Weight (kg) 65 65 (43–84) 66 68 (43–96)
Height (cm) 164 165 (152–180) NR
Body mass index (kg/m2) 25 24 (18–31) NR
Plasma creatinine (μmol/L)a 101 97 (66–156) 103 101 (48–165)
Estimated GFR (mL/min) 35 36 (21–45) 41 38 (22–82)
GFR glomerular filtration rate, NR not reported
a
Reference interval 60–100 μmol/L (men), 50–90 μmol/L (women)

Subjective image quality in either cohort. There was no significant difference

between the classifications made in the 200 mg I/kg cohort
Classification of subjective image quality is summerised in and those made in the 150 mg I/kg by observer 1 (p=1.0) or
Table 3. No examination was classified as non-diagnostic 2 (p=0.21).

Table 3 Outcome parameters in the present (150 mg I/kg) and the reference (200 mg I/kg) cohorts [9] undergoing 80-kVp 16-channel
multidetector computed tomography to diagnose acute pulmonary embolism in patients with moderate to severe renal impairment
150 mg I/kg (n=50) 200 mg I/kg (n=89)
Mean Median value (2.5 and 97.5 percentiles) Mean Median value (2.5 and 97.5 percentiles)
value value

Contrast medium dose

gI 9.6 9.6 (6.4–12) 13 13 (8.2–16)
mg I/kg 149 150 (129–160) 196 200 (160–207)
mg I/kg/s 12 13 (11–13) 13 13 (11–14)
g I/eGFR ratio 0.3 0.3 (0.2–0.4) 0.3 0.3 (0.2–0.6)
Injection rate (mL/s) 2.5 2.5 (1.7–3.2) 2.7 2.7 (1.7–3.3)
Pulmonary artery
Density (HU) 353 353 (164–495) 359 351 (199–563)
Noise (SD of HU) 29 26 (16–51) 24 23 (13–39)
CNR 11 11 (4.4–22) 13 12 (6.4–26)
Imaging time (s) 9 9 (7–12) NR
Imaging length (cm) 219 210 (172–294) NR
Effective tube loading (mAs) 265 255 (214–371) 277 255 (120–375)
CTDIvol (mGy) 5.8 5.6 (4.5–8.2) 6.1 5.6 (2.6–8.3)
Dose–length product (mGy cm)a 164 159 (125–215) 173 166 (74–247)
Effective dose (mSv)a 2.5 2.4 (1.9–3.2) 2.9 2.8 (1.3–4.2)
Subjective image quality Observer 1 Observer 2
Excellent 44% 34% 43%
Adequate 48% 54% 52%
Suboptimal 8% 12% 5%
Non-diagnostic 0% 0% 0%
CTDIvol volume pitch-corrected computed tomography dose index, CNR contrast-to-noise ratio providing a fresh clot measuring 70 HU,
eGFR estimated glomerular filtration rate, HU Hounsfield units, mAs milliampere second, mGy milligray, mSv millisievert, NR not reported,
SD one standard deviation
a
The second acquisition to ensure adequate enhancement of the thoracic aorta not included
1326
Fig. 2 Pulmonary artery density measured in Hounsfield units (HU)
(a) and contrast-to-noise ratio (b; assuming an embolic density of
70 HU) averaged between the left pulmonary artery and a lower lobe
segmental artery in relation to body weight in the present 150 mg I/
kg cohort
The two observers differed in their classification in 7 of
50 patients in the 150 mg I/kg cohort indicating good
agreement (kappa value of 0.76). If the classification was
dichotomized (adequate–excellent versus non-diagnostic–
suboptimal), they agreed in 48 of 50 patients and the kappa
value rose to 0.78. In five patients subjective image quality
was regarded excellent by observer 1, while observer 2
classified them as adequate. In the other two patients
subjective image quality was regarded adequate by
observer 1, but suboptimal by observer 2.
Image quality was regarded as suboptimal in four
patients by both observers and another two by observer
2. Suboptimal quality in four patients was due to various
combinations of high image noise (1 SD=36–50 HU),
artefacts secondary to inability to raise the arms above the
head (n=4), inability to hold respiration during the entire
examination (n=2), massive bilateral pleural effusion (n=
1) and pulmonary disease (n=1). Vascular density was
classified as suboptimal in the other two patients (density/
CNR 142 HU/3.1 and 150 HU/4.1, respectively). None of
these six patients had any further imaging tests and had no
VTE diagnosed during the 3 months’ follow-up, though
one patient had an extended 5 weeks’ prophylaxis with low
molecular weight heparin after a total knee replacement.
PE diagnosis and follow-up of negative CTPA
Seven patients (14%) had been diagnosed with CT-verified
PE at the time of the CT examination. During retrospective
analysis for subjective image quality no false-positive
diagnosis but one false-negative diagnosis of PE were
detected, a single small embolus in a segmental artery at the
bifurcation to its subsegmental branches. However,
3 months’ follow-up without anticoagulation was unevent-
ful. Among the 42 patient with a final negative CTPA, one
patient was on long-term anticoagulation because of atrial
fibrillation and one had an extended 5 weeks’ prophylaxis
with low molecular weight heparin after a total knee
replacement. None of the remaining 40 patients with a
negative CTPA and no anticoagulation was diagnosed with
VTE during the 3 months’ follow-up (upper 95% confidence
limit 8.8%). Eight (median age 86, range 78–97 years) of the
40 patients died during the follow-up period. The causes of
death according to the death certificates were pneumonia (n=
4), respiratory insufficiency (n=1), congestive heart failure
(n=1), lung cancer (n=1) and chronic lymphatic leukaemia
(n=1). None of them had undergone an autopsy. Subjective
image quality was judged as excellent in four, adequate in
three and suboptimal in one of them.
Contrast medium-induced nephropathy
Thirty-two patients had a plasma creatinine follow-up
within 1 week of CTPA. None of them had a plasma
creatinine rise more than 44.2 μmol/L. Another six patients
had a plasma creatinine follow-up more than 1 week after
CTPA, in five it was less than the baseline creatinine and in
one it had increased from 80 to 90 μmol/L. None of the
patients was diagnosed with severe CIN, i.e. oliguria/
anuria or requiring dialysis.
Discussion
Principal findings
Our results indicate that with the present 80-kVp 16-
MDCT technique it is possible to further decrease the CM
dose from 200 to 150 mg I/kg (25% reduction) in patients
with moderate to severe renal impairment, while preserving
diagnostic quality in terms of PA density and CNR in the
vast majority of patients. This was realised by cutting the
injection duration from 15 to 12 s resulting in approxi-
mately the same injected dose rate (≈13 mg I/kg/s). The
frequency of subjectively suboptimal examinations was in
line with that reported in the literature [20] and no patients
with a negative CTPA experienced any episodes of VTE
during follow-up. Only two patients had vascular density
classified as suboptimal, while the other main reasons for
suboptimal quality included artefacts due to the inability of

some elderly patients to hold their breath and/or to keep
their arms above the head.
With the present 80-kVp protocol the mean grams of
iodine/eGFR ratio was kept as low as 0.3:1 in the azotaemic
patients. A 1:1 g of iodine/eGFR ratio has been postulated as
an upper limit to minimise the risk of CIN after both CT and
coronary angiographic/angioplasty procedures in patients
without risk factors other than renal impairment [12, 21–23].
None of the patients who had serum creatinine follow-up
within 1 week in the present and the reference cohorts had
any evidence of CIN and none of the patients suffered
oliguria/anuria or required dialysis.
Results in relation to other studies
The present CM doses, ranging from 6–12 g iodine at
80 kVp, resulted in the same PA density as that reported
when using 120–140 kVp and non-individualised 24–
42 g of iodine doses with 16-MDCT [9, 24–26]. Tradi-
tional doses at 120–140 kVp may correspond to about
500 mg I/kg [26]. A recent study indicated that
400 mg I/kg is required using a 16-MDCT at 120 kVp
to reach a PA density of about 300 HU, which was
regarded adequate for assessing the diagnosis of PE [25].
Using the present technique it was possible to reach a
mean density of 353 HU using only 150 mg I/kg in
patients with moderate–severe renal impairment.
Sigal-Cinqualbre et al. were the first to suggest using
80 kVp to reduce the CM dose in chest CT for renal
protection [6]. Szucs-Farkas et al. used it primarily to
reduce radiation dose in CTPA by minimizing mAs
compensation [27, 28].
Contrast medium injection parameters
Decreasing the CM dose to a mean of only 9.6 g of iodine
was partially possible by individualising the dose relative
to body weight and using constant injection duration close
to the examination time rather than using a fixed CM dose
and injection rate for all patients [5]. In the latter instance
the injection time may far exceed the acquisition time.
Tailoring CM dose to body weight and using a fixed
injection time will result in a constant dose rate, i.e. a
constant delivery of a number of iodine atoms per kilogram
per second. Arterial enhancement should then be unrelated
to body weight [29]. However, PA density increased with
body weight in the present study, though the correlation
was weak. Though we used a dedicated computer program
for calculating individual CM volumes and injection rates,
this can easily be done with Microsoft Excel.
A 12-s injection time may at first sight seem to be too short
in some patients. The 4-s delay before initiating CT data
acquisition after the CM bolus reached the pulmonary
circulation leaves only an 8-s bolus train to cover CT
1327
acquisition, which ranged from 10 to 12 s in 14 patients.
However, in none of the patients did PA enhancement
diminish on the final images. One explanation may be the age
of the patient population with presumably a lower cardiac
output than normal, which slows down circulation time.
A certain number of patients definitely had a slow
circulation indicated by the fact that the CM had hardly
reached the thoracic aorta during the CTPA. To ensure proper
aortic enhancement, to avoid missing any differential
diagnoses such as aortic dissections/intramural haematoma,
we routinely perform a second thoracic 80-kVp imaging
procedure with a 7-s delay from the end of the first one. This
may be aborted by the CT radiographer if there is proper aortic
enhancement or obvious PE seen on-line during the first run.
To keep the imaging time as low as possible we limited
the cranio-caudal range of the CT examination and did not
include the most peripheral part of the pulmonary circu-
lation. Though small subsegmental PE may be missed by
this approach, follow-up studies of patients after negative
single- and multichannel detector CTPA using a similar
examination range strongly indicate that they may be safely
left without anticoagulation [30–32].
The presumed decreased cardiac output in the present
elderly population may also have had a positive impact on
vascular CM enhancement [33, 34]. At the same time
prophylactic hydration to avoid CIN in patients with poor
cardiac function is a problem. Such patients are therefore
particularly suitable for the low dose CM CTPA technique,
which may offer the best protection against CIN while
preserving diagnostic quality. However, in azotaemic
patients with a high cardiac output the present technique
may result in suboptimal enhancement, though this occurred
in only 2 of our 50 patients. To select azotaemic patients to
the low CM dose technique, it may be warranted to routinely
ask for an echocardiogram before the patient is sent for
the CTPA or to equip the CT suite with an electrical
velocimeter (Aesculon®, Osypka Medical GmbH, Berlin
Germany) [35, 36] to measure cardiac output immediately
prior to the examination.
Contrast-to-noise ratio
CNR is a key diagnostic index in detecting low-contrast
objects such as PE [8]. The density of clots may vary with
age and approach fluid density close to 0 HU [37]. When
calculating CNR we used a clot density of 70 HU
representing a fresh clot with a haematocrit close to
100% [16, 17] as a “worst-case scenario”. Using a clot
density of 70 HU, a CNR less than 5 resulted in suboptimal
subjective image quality in two of our patients. Although,
specific CNR values considered acceptable for a diagnostic
task are not generally available, our own experience and
that of others [8] indicate that a CNR of 5 is a minimum.
Image noise tended to increase with body weight. As PA
density also tended to increase, CNR showed only a weak
1328

tendency to decrease. The increase in image noise with body
weight may have two explanations. First, the automatic
exposure control undercompensates the required mAs adap-
tation to keep image noise constant in thicker patients [38].
Second, maximum tube loading at 80 kVp with the present
system is 380 mAseff using a rotation time of 0.5 s and a pitch
of 0.5. This sets a limit for the present CT equipment in obese
patients and the upper limit in our experience seems to be
about 90 kg. Recently developed more potent x-ray tubes and
dual-source CT may overcome this limitation.
Implications of 80-kVp CTPA
Two basic principles emerge on how to use a switch from
120–140 to 80 kVp CTPA to minimize dose complications,
i.e. contrast medium-induced nephropathy and radiation-
induced cancer, while keeping the diagnostic quality/CNR at
an appropriate level: (1) in the elderly nephro-vulnerable,
cardiac decompensated but relatively “radio-resistant” (with
regard to cancer induction) population by minimising CM
dose and compensating for increased noise with substantially
increased x-ray tube loading and (2) in the younger less
nephro-vulnerable, cardiac compensated but relatively more
radio-sensitive population by higher CM dose and no or only
minor increased x-ray tube loading for noise compensation.
sensitivity and specificity according to a gold standard.
However, no clinically significant PE seems to have been
missed, though fatal PE can not be excluded because of the
lack of autopsy in patients who died during follow-up. This
is a drawback typically shared with other PE management
studies [40]. No false-positive readings were encountered
during the subjective quality assessment.
Plasma creatinine follow-up was incomplete and should
ideally also be obtained within 48–72 h post-procedure [2].
CT studies using 27 to 40 g of iodine in patients with renal
impairment resulted in a mean CIN frequency of about 10%
[41–45]. Performing a clinical trial, that would reduce the CIN
frequency from 10% to 5% or 1% with the present low CM
doses and using a type I error of 5% and 80% power, would
need 456 and 105 patients, respectively, in each study arm.
CT venography following CTPA to diagnose deep venous
thrombosis in the case of a false-negative CTPA may not be
feasible with the present low CM doses [46]. However,
follow-up studies of negative CTPA alone in patients with
positive D-dimer or clinically likely PE indicate that routine
use of venous studies is not warranted [32, 47]. If a high
degree of suspicion of VTE still remains after a negative
CTPA, venous ultrasound may be performed.
Conclusion

When alternative imaging techniques not using iodine CM

Limitations
The present study suffers from the inherent limitations of
retrospective studies. However, the patient cohort was
prospectively and consecutively enrolled in a real-world
practice without many of the exclusion criteria encountered
in prospective scientific studies such as the PIOPED II
study [39]. Though we used a historical reference group, it
had similar characteristics with regard to gender ratio, age,
weight, height and renal function.
Subjective image quality was not evaluated by blinded
observers, which could have induced some bias. Our
evaluation was also limited to quantitative and qualitative
image criteria and not diagnostic accuracy in terms of
are inconclusive or unavailable to diagnose PE in azotaemic
patients, 80-kVp MDCT combined with reduced CM doses
tailored to body weight, a fixed injection duration adapted to
acquisition time, automatic bolus tracking and a saline chaser
may allow markedly reduced CM doses and preserved
diagnostic quality compared with common standards. This
should be to the benefit of patients at risk of CIN.
Acknowledgements Radiographers Lars Nilsson, Staffan Wettemark
and Anna Johansson for supervising the performance of the computed
tomography examinations. Jonas Björk, Ph.D., Competence Centre for
Clinical Research, University of Lund, University Hospital, Lund,
Sweden, for statistical advice. Librarian Elisabeth Sassersson, Lasarettet
Trelleborg, for excellent service regarding literature references.

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