Key words vascular - CT angiography - dual-energy computed tomography angiography - peripheral
artery occlusive disease - critical limb ischemia
Introduction
Digital subtraction angiography (DSA) is the traditional reference standard for diagnosing
peripheral artery occlusive disease (PAOD) of the lower extremities. DSA is not only
an excellent diagnostic tool for PAOD but is also a key for interventional treatment
of relevant artery stenoses under current therapy guidelines [1 ]
[2 ]. Nevertheless, DSA is an invasive procedure with potential complications [3 ] and so less invasive and more comfortable angiography techniques are desired when
imaging is primarily performed for diagnostic purposes or for therapy planning [4 ].
The status of lower extremity arteries in patients with suspected PAOD can be accurately
assessed with noninvasive computed tomography angiography (CTA). In two systematic
reviews with meta-analyses, single-source, single-energy multi-slice CT scanners (16-
and 64-MSCT) rendered sensitivities of 92 % and 95 %, respectively, and specificities
of 93 % and 96 %, respectively, for detecting arterial stenoses of more than 50 %
[5 ]
[6 ].
However, atherosclerotic calcifications may impede the assessment of arterial segments
on standard CTA images [7 ]. In small caliber arteries, calcified plaques may not be distinguishable from luminal
contrast enhancement impairing reliable stenosis grading and increasing interobserver
variability. CTA acquisitions in dual-energy technique (DE-CTA) are considered helpful
for ameliorating the drawback of limited tissue differentiation. DE-CTA scans allow
for better differentiation of contrast material, atherosclerotic plaques, and osseous
structures utilizing accentuated maximum density differences between 80 kV and 140 kV
[8 ]. DE-CTA image post-processing includes automated bone and atherosclerotic plaque
removal. Creation of multi-planar reconstructions or luminographic maximum intensity
projections (MIP) has thus proven to be less time-consuming than standard CTA scans
[11 ] and provides better visualization and characterization of vascular findings. Furthermore,
DE-CTA may be performed with lower contrast material doses in patients with reduced
kidney function due to the higher photoelectric effect at lower tube voltages. DE-CTA
scans do not necessarily lead to increased radiation exposure in comparison to standard
CTA scans, but may potentially reduce radiation, e. g. by calculating virtual native
images instead of additional non-contrast scans when endoleaks are sought [9 ].
The aim of this study was to assess the diagnostic accuracy of DE-CTA in comparison
to the diagnostic reference standard DSA. Because several existing studies have produced
promising and convincing results for DE-CTA in PAOD patients with rather mild or mixed
severity, we focused on patients with critical limb ischemia or severe symptoms of
PAOD. In addition, we assessed the influence of atherosclerotic calcifications, image
quality, and the presence and types of artifacts on the diagnostic accuracy of DE-CTA,
which still are not sufficiently valued and studied aspects for potential image limitations.
Furthermore, we evaluated the interobserver agreement of the DE-CTA readers.
Materials and methods
Subjects
The local ethics committee approved this retrospective diagnostic study (petition
no. 80/09). Patients who were referred for runoff DE-CTA of the pelvis and the lower
limbs due to clinical symptoms of peripheral arterial occlusive disease (PAD) between
01/2008 and 09/2009 were retrospectively selected for this study. The patients were
included in the study if they had an additional digital subtraction angiography of
the same body region within 30 days after the DE-CTA scan. [Fig. 1 ] shows the patient selection process in a flow chart.
Fig. 1 Patient selection flowchart.Abb. 1 Flussdiagramm der Patientenselektion.
In all, 99 DE-CTA studies of 94 consecutive patients (mean age: 72.7 years; age range:
40 – 96; female: 32; male: 62) with subsequent DSA could be included in the study,
resulting in 198 extremities for evaluation. In 5 patients, DE-CTA and DSA scans were
repeated during the study period due to recurrent symptoms of PAOD. The degree of
PAOD, classified according to clinical symptoms as described by Fontaine [10 ], was documented in 123 of the 198 cases. None of the cases were stage I, 1 case
was stage IIa, 16 cases were stage IIb, 27 cases were stage III, and 79 cases were
stage IV.
Dual-energy CT angiography
Runoff DE-CTA was performed using a first-generation 64-slice dual-source CT scanner
(Somatom Definition; Siemens Healthcare, Forchheim, Germany) applying the following
parameters: tube voltages: 140 and 80 kV; effective tube current: 50 (140kVp) and
270 mAs (80kVp); collimation: 64 × 1.2 mm; gantry rotation time: 0.5s; table movement:
40 mm/s; and pitch factor: 1.0. Patients were scanned feet-first in supine position.
Pre-warmed contrast material (Ultravist 370, Bayer Schering Pharma, Leverkusen, Germany)
was automatically injected via an antecubital 18-gauge vein catheter at a flow rate
of 4.0 ml/s. CT acquisition was initiated using the Care Bolus technique when the
mean density within an region-of-interest (ROI) reached the level of 150 Houndsfield
Units (HU) during contrast material injection of 80 ml with a delay of 5 s. The runoff
scan covered the volume between the infrarenal aorta and the toes.
CT image post-processing
CT images were reconstructed in axial orientation with a slice thickness of 1.5 mm
and an increment of 1.0 mm using filtered back-projection and a medium vessel kernel.
Axial reconstructions were further post-processed using the dual-energy application
(VE25A, Siemens Healthcare, Germany). The dual-energy software application removed
bone and rendered the automated removal of calcified plaques due to spectral differences
from luminal iodine enhancement ([Fig. 2 ]). Specific absorption characteristics at 80 and 140 kVp allow for differentiation
of calcified structures and iodine. First, axial images were automatically combined
to 80 kVp/140 kVp images with weighting of 60 %/40 %. Axial MPRs with these settings
were generated and used for evaluation. Secondly, three-dimensional maximum intensity
projections (MIPs) after automatic bone and plaque removal were generated with a 180°
circumference in 10° increments. These MIPs were part of the image assessment. Both
axial MPRs and 3 D MIPs had been sent to the PACS and were evaluated by two CTA readers.
Fig. 2 The software automatically renders the subtraction of bones and plaques from non-processed
80/140 kVp dual-energy images. Coronal MIPs and axial MPR images at the level of the
proximal lower leg demonstrate the post-processing from non-processed images A , B to images after bone removal C , D and after bone and plaque removal E , F . The cross-sections reveal occlusion of the proximal ATA and contrast-enhanced lumens
of PTA and FA.Abb. 2 Die Software vollführt eine automatische Subtraktion der knöchernen Strukturen und
der Kalkplaque von den nicht-verarbeiteten 80 / 140 kVp Dual-energy Bildern. Koronare
MIPs und axiale MPR Bilder auf Höhe des proximalen Unterschenkels zeigen die Nachverarbeitung
von den nicht-verarbeiteten Bildern A , B , über die Bilder nach Entfernung der knöchernen Strukturen C , D und nach zusätzlicher Plaqueentfernung E , F . Die Querschnittsbilder zeigen einen Verschluss der proximalen A. tibialis anterior
und eine Kontrastierung der A. tibialis posterior und fibularis.
Digital subtraction angiography
Digital subtraction angiography (DSA) was considered the diagnostic gold standard.
The mean time interval between DSA acquisition and the DE-CTA scan was 7.1 days (range:
0 – 29 days). Images were acquired using the DSA unit “Artis Zee Heeling” combined
with Syngo imaging software (Siemens Healthcare, Erlangen, Germany). DSA was performed
for interventional or surgical therapy planning.
The femoral artery of the non-/less-symptomatic lower limb was accessed in retrograde
direction after local anesthesia (mepiracain; Scandicain, Astra Zeneca, Wedel, Germany)
using an 18-gauge puncture needle, when pelvic segment stenosis could not be excluded.
A 5F pigtail catheter was introduced via a 5F introducer sheath (Avanti Plus, Cordis
Corp., Bridgewater, NJ) over guidewire and placed in the infrarenal abdominal aorta.
In other cases, lower extremity arteries were accessed via an antegrade puncture of
the common femoral artery of the diseased extremity. Contrast material (Ultravist
300, Bayer Schering Pharma, Leverkusen, Germany) was either automatically injected
using the angiographic injection system (Mark V ProVis, Medrad Europe, Netherlands)
at a flow rate of 15 ml/s for the pelvis region (30 ml), or manually for peripheral
projections (10 ml). At the pelvis level, images were acquired in posterior-anterior
(PA), and oblique (30°) PA views with a frame rate of 2 images per second. The proximal
thigh was imaged in PA and oblique PA views with 1 frame per second. The lower leg
and feet were imaged in PA/oblique PA/parallel to the plane of the interosseous membrane
with a frame rate of 1 per second.
Image assessment
Two radiologists with 12 and 8 years of experience in diagnostic vascular imaging
reviewed DE-CTA images. Both readers assessed images independently and were blinded
to all clinical information and radiological imaging and reporting. A third independent
reader, an interventional radiologist with 11 years of experience, reviewed all DSA
images. This reader was blinded to DE-CTA images, but had access to clinical and therapy
information. The findings documented by this reader were considered the diagnostic
reference standard. All readers evaluated images on a PACS workstation (IMPAX, Agfa
HealthCare, Germany).
Criteria for segmental assessment of arteries
The aorta and the arteries of the pelvis and the lower extremities were subdivided
into 15 segments: Infrarenal abdominal aorta (IAA), common iliac artery (CIA), internal
iliac artery (IIA), external iliac artery (EIA), common femoral artery (CFA), femoral
artery bifurcation (FAB), superficial femoral artery (SFA), profound femoral artery
(PFA), popliteal artery (PA), anterior tibial artery (ATA), tibial-fibular trunk (TFT),
posterior tibial artery (PTA), fibular artery (FA), dorsal pedal artery (DPA), and
plantar pedal artery (PPA). The arterial segments were grouped into the following
vessel regions: Pelvis (CIA, IIA, EIA), above knee (CFA, FAB, SFA, PFA, PA), below
knee (ATA, TFT, PTA, FA), and foot (DPA, PPA).
The DSA reader and the two DE-CTA readers and the DSA reader reviewed and evaluated
each arterial segment of all patients according to the following evaluation criteria:
The degree of stenosis was subjectively determined by estimating the percentage of
lumen reduction in relation to the proximally adjacent non-stenotic lumen. Stenoses
were categorized as no stenosis, stenosis of less than 50 %, stenosis of 51 % to 70 %,
stenosis of 71 % to 99 %, and occlusion.
Calcifications were categorized as no calcifications, minor calcifications that involved
less than 1/3 of the lumen circumference, moderate calcifications that involved between
1/3 and 2/3 of the lumen circumference, and severe calcifications that involved more
than 2/3 of the lumen circumference.
Image quality was subjectively evaluated taking the depiction of anatomical structures,
image contrast and resolution, and limitations due to artifacts into account. Image
quality was categorized into not adequate, acceptable, good, and excellent. Image
quality was assessed per vascular region.
Image artifacts were categorized as no artifacts, artifacts without limitation of
image interpretation, and artifacts with limitation of image interpretation.
The following types of artifacts were documented: suboptimal vessel enhancement, motion
artifacts, venous contamination, beam-hardening artifacts, and other artifacts (e. g.
stent artifacts).
Processing and analyses of findings and results
All findings and results of both CTA readers were separately compared to the results
of the DSA reader.
Incidence analyses
Incidences of arterial stenosis and atherosclerotic calcifications were documented
for each arterial segment. Arterial stenoses of > 50 % were considered a positive
finding. Furthermore, image quality as well as the presence and type of imaging artifacts
were documented. Results were summarized in contingency tables and presented per segment
or grouped per extremity or arterial region. Extremities or regions were considered
“stenosis-positive” if at least one arterial segment had a positive finding. When
arterial segments were not assessable because they were not included in the scanned
volume, e. g. due to prior amputation, segments were rejected. When arterial segments
were not assessable due to limited image quality, e. g. beam hardening artifacts due
to metal implants, segments were also rejected. All calculations were performed per
leg, per region, and per arterial segment.
Statistical analyses
Diagnostic performance
The diagnostic performance of DE-CTA for the detection of arterial stenoses of > 50 %
was assessed in comparison to the diagnostic reference standard DSA. Sensitivity,
specificity, and likelihood ratios were calculated for each reader. These calculations
required matching of the arterial segments displayed on DE-CTA and DSA images. When
arterial segments could not be matched, for example if they were not visualized, they
were rejected from analysis.
Impact of calcifications, image quality, and image artifacts on the diagnostic performance
of DE-CTA
Fisher’s exact test was performed to test whether atherosclerotic calcifications,
image quality, the presence of artifacts, and the type of artifact had a significant
influence on the diagnostic accuracy of DE-CTA.
Interobserver agreement and further statistical analyses
Interobserver agreement was assessed using Kappa statistics [11 ]. Interobserver agreement was considered almost perfect for ĸ = 0.81 – 1.0, substantial
for ĸ = 0.61 – 0.8, moderate for ĸ = 0.41 – 0.6, fair for ĸ = 0.21 – 0.4, and slight
for ĸ = 0 – 0.2. Calculations and further statistical analyses were performed using
the SPSS (Version 21.0, IBM, USA) and Prism (Version 6.0c, GraphPad Software, USA).
P-values of < 0.05 were considered statistically significant. When results for both
observers are given, the first is the result of reader 1, and the second the result
of reader 2.
Results
Incidence analysis
Degree of stenosis
[Table 1 ] illustrates the frequency distribution for the degree of stenosis detected on DE-CTA
by each observer in comparison to DSA for all evaluable 1014 artery segments. DE-CTA
led to fewer stenosis exclusions than DSA, while occlusions were found in a comparable
number of arterial segments. The interobserver evaluation of both readers for detecting
stenoses of > 50 % resulted in strong agreement for all arteries (ĸ = 0.623). The
agreement was substantial in the pelvis region (ĸ = 0.556), strong in the thigh region
(ĸ = 0.639), substantial in the lower leg region (ĸ = 0.565), and fair in the foot
region (ĸ = 0.362).
Table 1
Stenosis degree of artery segments. Incidence comparison of DE-CTA versus DSA. The
table show the results of the first reader only. The second reader had similar results.
Kappa values for the determination of the interobserver agreement are given in the
text.Tab. 1 Stenosegraduierung in den arteriellen Segmenten. Vergleich der Inzidenzen bei der
DE-CTA und der DSA. Die Tabelle zeigen nur die des ersten Auswerters, der zweite Auswerter
erzielte vergleichbare Ergebnisse. Die Kappa Werte zur Einschätzung der Auswerterübereinstimmung
sind im Text genannt.
DSA
degree of stenosis
not assessable
not visualized
none
< 50 %
50 – 70 %
71 – 99 %
occlusion
SUM
[%]
DE-CTA
degree of stenosis
none
362
22
3
15
22
3
0
427
42.1
< 50 %
52
10
1
8
0
1
0
72
7.1
50 – 70 %
48
9
8
6
4
0
0
75
7.4
71 – 99 %
89
19
7
42
55
8
0
220
21.7
occlusion
33
3
0
14
149
14
0
213
21
not assessable
3
0
0
0
2
0
0
5
0.5
not visualized
2
0
0
0
0
0
0
2
0.2
SUM
589
63
19
85
232
26
0
1014
[%]
58.1
6.2
1.9
8.4
22.9
2.6
0
Degree of calcification
[Table 2 ] shows the severity distribution for segmental artery calcifications detected on
DE-CTA by each observer in comparison to DSA for all evaluable 1014 artery segments.
The readers detected more calcifications and a greater extent of calcification using
DE-CTA in comparison to DSA. The interobserver agreement of both readers was substantial
(ĸ = 0.518). The regional interobserver agreement was substantial in the pelvis region
(ĸ = 0.457), substantial in the thigh region (ĸ = 0.451), and fair in the lower leg
and foot region (ĸ = 0.359).
Table 2
Degree of calcification. Incidence comparison of DE-CTA versus DSA. The table show
the results of the first reader only. The second reader had similar results. Kappa
values for the determination of the interobserver agreement are given in the text.Tab. 2 Verkalkungsgrad. Vergleich der Inzidenzen bei der DE-CTA und der DSA. Die Tabelle
zeigen nur die des ersten Auswerters, der zweite Auswerter erzielte vergleichbare
Ergebnisse. Die Kappa Werte zur Einschätzung der Auswerterübereinstimmung sind im
Text genannt.
DSA
degree of calcification
not assessable
not visualized
none
< 1/3
1/3 – 2/3
> 2/3
SUM
[%]
DE-CTA
degree of calcification
none
322
39
5
1
4
0
371
36.6
< 1/3
145
18
5
1
3
0
172
17.0
1/3 – 2/3
47
10
0
0
0
0
57
5.6
> 2/3
243
84
43
16
21
0
407
40.1
not assessable
2
1
2
0
0
0
5
0.5
not visualized
2
0
0
0
0
0
2
0.2
SUM
761
152
55
18
28
0
1014
[%]
75.0
15.0
5.4
1.8
2.8
0.0
Image quality
[Table 3 ] demonstrates the frequency distribution of image quality of DE-CTA in comparison
to DSA for all evaluable 252 regions. The interobserver agreement of both readers
was poor (ĸ = 0.017). Reader 1 considered the quality of 160 regions excellent, 77
regions good, 11 regions acceptable, and 4 not adequate. Reader 2 considered the quality
of 24 regions excellent, 183 good, 39 acceptable, and 6 not adequate. [Table 4 ] demonstrates the frequency distribution for the presence and degree of imaging artifacts
detected on DE-CTA by each observer in comparison to DSA for all evaluable 1014 segments.
The interobserver agreement of both readers was fair (ĸ = 0.225). The categorization
of artifacts is given in [Table 5 ]. The most common artifact of DE-CTA was venous contrast material contamination at
the acquisition time point found in 5.8 % of arterial segments. The interobserver
agreement of both readers was fair (ĸ = 0.257).
Table 3
Image quality. Incidence comparison of DE-CTA versus DSA. The table show the results
of the first reader only. The second reader had similar results. Kappa values for
the determination of the interobserver agreement are given in the text.Tab. 3 Bildqualität. Vergleich der Inzidenzen bei der DE-CTA und der DSA. Die Tabelle zeigen
nur die des ersten Auswerters, der zweite Auswerter erzielte vergleichbare Ergebnisse.
Die Kappa Werte zur Einschätzung der Auswerterübereinstimmung sind im Text genannt.
DSA
not adequate
acceptable
good
excellent
SUM
[%]
DE-CTA
not adequate
0
0
0
4
4
1.6
acceptable
0
0
0
11
11
4.4
good
3
1
2
71
77
30.6
excellent
0
0
3
157
160
63.5
SUM
3
1
5
243
252
[%]
1.2
0.4
2.0
96.4
Table 4
Presence of image artifacts. Incidence comparison of DE-CTA versus DSA. The table
show the results of the first reader only. The second reader had similar results.
Kappa values for the determination of the interobserver agreement are given in the
text.Tab. 4 Präsenz von Bildartefakten. Vergleich der Inzidenzen bei der DE-CTA und der DSA.
Die Tabelle zeigen nur die des ersten Auswerters, der zweite Auswerter erzielte vergleichbare
Ergebnisse. Die Kappa Werte zur Einschätzung der Auswerterübereinstimmung sind im
Text genannt.
DSA
artifacts
not assessable
not visualized
none
present without limitation
present with limitation
SUM
[%]
DE-CTA
artifacts
none
877
6
10
13
0
906
89.3
present without limitation
70
0
6
1
0
77
7.6
present with limitation
28
0
0
0
0
28
2.8
not assessable
1
0
0
0
0
1
0.1
not visualized
2
0
0
0
0
2
0.2
SUM
978
6
16
14
0
1014
[%]
96.4
0.6
1.6
1.4
0.0
Table 5
Type of artifacts. Incidence comparison of DE-CTA versus DSA. The table show the results
of the first reader only. The second reader had similar results. Kappa values for
the determination of the interobserver agreement are given in the text.Tab. 5 Artefakttypen. Vergleich der Inzidenzen bei der DE-CTA und der DSA. Die Tabelle zeigen
nur die des ersten Auswerters, der zweite Auswerter erzielte vergleichbare Ergebnisse.
Die Kappa Werte zur Einschätzung der Auswerterübereinstimmung sind im Text genannt.
DSA
type of artifact
not assessable
not visualized
suboptimal enhancement
motion
venous contamination
beam-hardening
other
none
SUM
[%]
DE-CTA
type of artifact
suboptimal enhancement
0
0
0
0
0
12
0
0
12
1.2
motion
0
0
0
0
0
7
0
0
7
0.7
venous contamination
6
0
0
0
0
52
1
0
59
5.8
beam-hardening
0
0
0
0
0
0
0
0
0
0.0
other
0
0
0
0
0
27
0
0
27
2.7
none
16
0
0
0
0
877
13
0
906
89.3
not assessable
0
0
0
0
0
1
0
0
1
0.1
not visualized
0
0
0
0
0
2
0
0
2
0.002
SUM
22
0
0
0
0
978
14
0
1014
[%]
2.2
0.0
0.0
0.0
0.0
94.6
1.4
0.0
Diagnostic accuracy
The sensitivity of DE-CTA for the detection of stenosis of any degree was 85.3 % and
the specificity was 68.9 % in comparison to DSA for observer 1, and 74.4 % and 77.0 %
for observer 2. The diagnostic accuracy was 74.5 % for observer 1 and 77.0 % for observer
2. [Table 6 ] demonstrates that the diagnostic accuracy of DE-CTA increases when the test was
considered positive for true-positive stenosis of > 50 % in at least one arterial
segment per extremity, and negative for stenoses of < 50 %. Here, the two observers
produced a mean sensitivity of 96 % and a mean specificity of 71 %. The diagnostic
accuracy evaluation of arterial regions given as means of both observers resulted
in a sensitivity of 73 % and a specificity of 70 % at the pelvis level, a sensitivity
of 90 % and a specificity of 79 % at the thigh level, a sensitivity of 86 % and a
specificity of 49 % at the lower leg level, and a sensitivity of 77 % and a specificity
of 54 % at the pedal level. [Table 7 ] shows the diagnostic accuracy of DE-CTA for each arterial segment. The diagnostic
accuracy decreased from proximal to distal with the exception of the internal iliac
artery (IIA),
Table 6
Diagnostic accuracy of DE-CTA in comparison to the diagnostic reference standard DSA.
An extremity was considered disease-positive when it included at least one true-positive
arterial segment.Tab. 6 Diagnostische Genauigkeit der DE-CTA im Vergleich zum diagnostischen Referenzstandard
DSA. Bei der Auswertung pro Extremität wurde die Extremität dann als erkrankt angesehen,
wenn diese mindestens ein „richtig-positives“ Segment aufwies.
TP
TN
FP
FN
Sens
[%]
Spec
[%]
LR+
LR–
extremity assessment
R1
97
9
3
2
97.98 %
75.00 %
3.92
0.03
R2
93
8
4
6
93.94 %
66.67 %
2.82
0.09
R1 + R2
190
17
7
8
95.96 %
70.83 %
3.29
0.06
arterial segment assessment
R1
285
446
201
49
85.33 %
68.93 %
2.75
0.21
R2
238
499
138
82
74.38 %
78.34 %
3.43
0.33
R1 + R2
523
945
339
131
79.97 %
73.60 %
3.03
0.27
Abbr.: R: reader; TP: true positive, TN: true negative, FP: false positive; FN: false
negative; Sens: sensitivity; Spec: specificity; LR: likelihood ratio.
Table 7
Diagnostic accuracy of DE-CTA grouped by arterial segment in comparison to the diagnostic
reference standard DSA. Diagnostic accuracy decreases from proximal to distal. The
arterial segment size and the vessel course orthogonal to the axial CTA image plane
seem to have particular influence on diagnostic accuracy.Tab. 7 Die diagnostische Genauigkeit der DE-CTA gruppiert nach arteriellen Segmenten im
Vergleich zum diagnostischen Referenzstandard DSA. Die diagnostische Genauigkeit nimmt
von proximal nach distal ab. Die Größe des arteriellen Segmentes und ein möglichst
orthogonaler Verlauf zur axialen CTA Bildebene scheinen einen wesentlichen Einfluss
auf die diagnostische Genauigkeit zu haben.
reader 1
reader 2
artery
Sens[%]
Spec[%]
Acc[%]
n
Sens[%]
Spec[%]
Acc[%]
n
ĸ
AA
100
75
76
34
100
100
100
34
0.145
CIA
71
81
78
41
79
92
88
40
0.64
IIA
75
35
40
35
75
45
49
35
0.479
EIA
70
90
85
39
90
83
85
39
0.584
CFA
100
89
89
76
100
91
91
76
0.59
FAB
100
94
94
85
100
92
92
85
0.451
SFA
91
62
75
83
86
82
84
93
0.382
PFA
40
83
80
86
40
88
85
87
0.659
PA
100
55
65
82
94
63
70
82
0.552
TFT
93
38
59
76
81
45
59
71
0.639
ATA
86
50
74
73
36
82
60
69
0.708
PTA
88
61
74
57
88
56
84
53
0.355
FA
92
50
86
72
30
79
46
68
0.728
DPA
69
43
60
60
30
79
46
56
0.365
PPA
83
52
65
72
75
71
72
69
0.487
Abbr.: Sens: sensitivity; Spec: specificity; Acc: accuracy; n: number of segments.
Impact of calcifications, image quality, and image artifacts on the diagnostic performance
of DE-CTA
The impact of calcifications, image quality, and image artifacts on the sensitivity
and specificity of DE-CTA was evaluated using Fisher’s exact tests. The degree of
calcification had a significant influence on both the sensitivity and specificity
of DE-CTA. Fisher’s Exact tests resulted in p = 0.005 for DSA-positive and p < 0.001
for DSA-negative segments (reader 1), and in p < 0.001 for both DSA-positive and DSA-negative
segments (reader 2). Reader 1 achieved a sensitivity of 91.1 % for strongly calcified
(grade 4) and 70.0 % for minimally calcified arterial segments. The specificity decreased
from 81.2 % to 46.2 % with an increasing degree of calcification.
The image quality did not significantly influence the sensitivity. However, the specificity
significantly increased with a higher image quality from 70.0 % to 76.4 %. Fisher’s
Exact tests resulted in p = 0.3287 for DSA-positive and p < 0.001 for DSA-negative
segments (reader 1), and in p < 0.396 for DSA-positive and p = 0.004 for DSA-negative
segments (reader 2).
Image artifacts, categorized as suboptimal enhancement, motion artifacts, venous contamination,
beam-hardening, or other artifacts, did not significantly influence the sensitivity
or specificity of reader 1 ([Table 5 ]). However, artifacts that limited the image interpretation of reader 2 decreased
his specificity. Fisher’s Exact tests resulted in p = 0.807 for DSA-positive and p < 0.623
for DSA-negative segments (reader 1), and in p < 0.057 for DSA-positive and p < 0.001
for DSA-negative segments (reader 2).
Discussion
DE-CTA is helpful in the diagnosis of PAOD in comparison to the traditional diagnostic
reference standard DSA. The two observers had sensitivities of 98.0 % and 93.9 % and
specificities of 75.0 % and 66.7 % for detecting stenoses of > 50 % of the lower extremity
arteries.
Two other comparable studies have been published with smaller collectives, in which
DE-CTA was evaluated in comparison to DSA [12 ]
[13 ]: In the study of Brockmann et al., almost equivalent sensitivity of 97.2 % was achieved.
The reported specificity of 94.1 % was higher than that of the readers of our study.
Probable reasons for this difference may be the selection of a 70 % stenosis level
for relevant disease, and the exclusion of the pedal arteries from their analysis.
Furthermore, our study includes significantly more patients at a progressed disease
stage or critical limb ischemia. We included 79 (84 % of n = 94) patients with Fontaine
stage 4 in comparison to 6 (30 % of n = 20) patients. In the study of Kau et al.,
the authors reported good sensitivity of 84 % and moderate specificity of 67 % for
a cohort of 58 patients. They also included the pedal arteries, and, like us, described
low diagnostic accuracy of DE-CTA for these arterial segments. Both studies primarily
focused on maximum intensity projections (MIPs) for assessing arterial segments, whereas
axial reconstructions and MIPs were used in the presented study. Several other studies
of CTA in the diagnosis of PAOD have revealed good to excellent accuracy for mono-energetic
acquisitions [6 ]
[14 ]
[15 ]
[16 ]
[17 ]. Among these, extremely high sensitivities of 99 % and specificities of 98 % were
reported in two studies. At first glance, these numbers obviously call into question
the necessity for the dual-energy technique. In the first study on 41 patients with
critical limb ischemia, pedal arteries were excluded from analysis. Furthermore, the
methodology was not designed for assessing extremely calcified, inadequately opacified,
or artifact-afflicted segments [18 ]. In the second study on 28 patients with a predominately intermediate disease stage,
the methodology lacks precision regarding the inclusion of pedal arteries, the rejection
of inappropriately visualized segments, as well as the independence and the interobserver
agreement of the cardiologists interpreting the CTA images [17 ]. Overall, we had higher diagnostic accuracy for proximal than for distal arterial
segments, but observed an accuracy drop for the IIA. This may be explained by a more
tortuous vessel course.
DE-CTA overestimated the number of relevant artery stenoses in comparison to DSA ([Table 1 ], [Fig. 3 ]). DSA excluded relevant disease in 652 (64.2 %) arterial segments, DE-CTA in only
499 (49.2 %). The number of occlusions was comparable (DSA, 232, DE-CTA, 213). These
observations can be explained by the significant impact of calcifications on stenosis
degree interpretation. We observed a decrease in specificity in highly calcified segments.
In these segments the sensitivity increased potentially due to the higher probability
and incidence of positive findings. Furthermore, DE-CTA displayed more and stronger
calcifications than DSA. Calcifications were excluded in 761 (75 %) of arterial segments
by DSA and in 371 (36 %) segments by DE-CTA. In contrast, severe calcifications were
detected in 407 (40.1 %) segments by DE-CTA and in 18 (1.8 %) segments by DSA. At
the lower extremities, it is well known that CTA renders direct and sensitive depiction
of calcified plaques around the vascular circumference. This results in higher precision
for plaque assessment than DSA and renders plaque characterization and composition
analysis. However, calcified plaques can impair the evaluation of the vascular lumen
and precise stenosis grading. In strongly calcified arteries or in atherosclerotic
segments below the knee, CTA reporting thus requires more intensive and time-consuming
image post-processing and evaluation. As calcifications also had a strong impact on
the accuracy of DE-CTA, the resulting decrease in specificity may lead to a number
of patients undergoing invasive DSA for therapeutic reasons without having relevant
stenosis.
Fig. 3 The stenosis degree can be overestimated on coronal MIP images with bone and plaque
removal (left image) as well as on axial combined DE images (extract within the left
image) in comparison to the reference standard DSA (right images). In this patient,
DE-CTA images led to the assumption of a high-grade stenosis of the proximal superficial
femoral artery, whereas the DSA image demonstrates lumen narrowing of < 50 %.Abb. 3 Der Stenosegrad kann auf koronaren MIP Bildern mit Knochen- und Plaqueentfernung
(linkes Bild) sowie auf axialen, kombinierten DE-Bildern (Ausschnitt im linken Bild)
im Vergleich zur DSA überschätzt werden. Bei diesem Patienten wurde anhand der DE-CTA
Bilder eine hochgradige Stenose der proximalen A. femoralis superficialis vermutet,
während die DSA eine Lumeneinengung von < 50 % zeigte.
The image quality of DE-CTA was good in 63.5 % of images and excellent in 30.6 %.
DSA images were considered to have excellent quality in 96 % of cases, probably due
to potential repetitions of DSA acquisitions. Impaired quality of DE-CTA images significantly
reduced the specificity. Images were free of artifacts in 96.4 % of DSA and 89.3 %
of DE-CTA acquisitions. The 7.7 % more artifacts on DE-CTA images were due to suboptimal
enhancement, motion or venous contamination. Surprisingly, artifacts did not necessarily
lead to limitations of image interpretation. While most artifacts may be avoided using
DSA by just repeating the acquisition and only sending the optimal image to the PACS,
DE-CTA is normally performed without repetitions in order to limit radiation exposure
and the amount of applied contrast material. Suboptimal contrast enhancement or venous
contamination is mostly unavoidable using DE-CTA when non-time-resolved acquisitions
are performed. Several studies have given recommendations for optimal contrast material
concentration, amount, and injection rate as well as CT acquisition parameters that
lead to improved, artifact-deprived image quality [19 ]
[20 ]. In our study, rather low volumes of contrast agent were applied in a fixed protocol
in comparison to other studies [12 ]
[21 ]. The DE-CTA technique allows for reduced contrast material concentrations utilizing
the abundant photoelectric effect at lower tube voltages [22 ]. Thus, the DE-CTA technique may be performed with a lower risk of contrast material-induced
nephropathy. The reduction of this risk is important, as advanced PAOD is frequently
found in patients with diabetes mellitus and concomitant nephropathy.
In our study, patients were scanned using a dual-source dual-energy CT machine from
the first generation. Recently, a third-generation scanner was introduced. The technical
developments include improved X-ray detectors providing higher resolution and better
image quality due to reduced electronic noise [23 ]. Furthermore, iterative reconstruction algorithms have been incorporated by most
vendors that increasingly replace the filtered back-projection algorithms as they
allow for reduced radiation doses and higher image quality due to a reduction of image
noise [24 ]. However, the impact of iterative reconstruction on CTA of the lower extremities
requires evaluation as it has been shown that the quantification of calcified coronary
artery plaques may be impaired with increasing iteration levels [25 ].
Our study was limited by its retrospective design. Differences in diagnostic accuracy
in comparison to other studies may result from a selection bias. DE-CTA scans had
not been performed for study purposes, but in the clinical routine and may have resulted
in predominantly high disease stages of PAOD or critical limb ischemia. Furthermore,
accompanying diseases such as diabetes mellitus or renal insufficiency as well as
specific demographics could not have been previously selected. All patients have had
high treatment probability; otherwise the invasive DSA procedure would not have been
indicated. None of our patients had been examined for only diagnostic purposes. DSA
series had been acquired for the diseased extremity only, usually not for both sides.
The retrospective study design did not allow control of the vascular access technique,
which had been individually chosen using an antegrade direct or retrograde cross-over
puncture technique. This resulted in a lower number of matching aorta and pelvis segments
on DE-CTA and DSA images. A selection bias may also have occurred, when excluding
arterial segments from evaluation due to e. g. image artifacts. The total contrast
material volume was 80 ml for DECTA studies, and 80 – 90 ml for DSA studies. However,
we have not documented the individual volume for each DSA study. The methodology was
partly based on subjective evaluation criteria. This may have resulted in limited
precision of measurements and variability in grading scales, but reflects real-world
conditions and allows for the assessment of interobserver agreement in clinical routine
processes. The number of observers, two independent CTA readers and one DSA reader,
may have resulted in a further bias. Finally, we considered a lumen reduction of > 50 %,
which is a frequently used cut-off value in the literature, to be a stenosis-positive
finding [5 ]. One may consider stenoses of > 70 % clinically relevant, whereas the true hemodynamic
relevance can be assessed by measuring pressure gradients. The yield of DECTA may
have been overestimated and may have resulted in concordance of both readers, as we
assessed stenotic lesions per segment and region, but not each particular lesion.
DSA may have displayed more findings than DE-CTA, when unperceived embolic events
have occurred during the period between the two studies. Finally, we haven’t documented
or evaluated radiation doses for study purposes of the DE-CTA scans. Patients were
scanned with DE tube voltage settings of 140 and 80kVp and effectively exposed to
50 and 270 mAs, respectively. These acquisition parameters were comparable to that
of other studies, e. g. DE-CTA studies with the identically constructed CT machine
exposing 56 mAs at 140 kVp and 238 mAs at 80 kVp resulted in a mean CTDIvol of 4.1 mGy
(range: 2.8 – 6.2 mGy) [21 ]. The scan time of the CTA studies was not documented, as we did not consider this
parameter relevant for our conclusions.
Conclusion
DE-CTA is accurate in the detection of lower extremity artery stenoses of > 50 % in
symptomatic POAD patients. Atherosclerotic calcifications, image quality, and artifacts
did not significantly influence the sensitivity of DE-CT, but atherosclerotic calcifications
significantly reduced and artifacts partly reduced the specificity of DE-CTA. The
overall interobserver agreement ranged between moderate and substantial for stenosis
detection and calcified plaque assessment.
Clinical relevance of this study
The diagnostic accuracy of DE-CTA plays a key role for justifying its implementation
as a noninvasive, pre-interventional imaging modality in the diagnostic workup of
patients with critical limb ischemia or severe disease stage.
Difficulties or limitations in the interpretability of CTA images often experienced
in patients with progressed POAD and severe calcifications may be facilitated using
dual-energy CTA acquisitions.
Despite the benefits of bone and plaque removal on DE-CTA images, diagnostic specificity
can be impeded by atherosclerotic calcifications and imaging artifacts.
