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Int J Cardiovasc Imaging (2017) 33:731–737
DOI 10.1007/s10554-016-1049-z
Visualizing polymeric bioresorbable scaffolds withthree-
dimensional image reconstruction using contrast-enhanced micro-
computed tomography
ShengTu
1
· FudongHu
2
· WeiCai
1
· LiyanXiao
3
· LinlinZhang
1
· HongZheng
1
·
QiongJiang
1
· LianglongChen
1
Received: 12 September 2016 / Accepted: 20 December 2016 / Published online: 30 December 2016
© The Author(s) 2016. This article is published with open access at Springerlink.com
the contrast agent soaking time was more than 2h (Treat-
ment-3 and -4). By setting 10–15 HU as a cut-point of CT
values, the scaffold strut detectable rate at Baseline and
Teatment-1, -2, -3 and -4 were 1.23 ± 0.31%, 1.65 ± 0.26%,
58.14 ± 12.84%, 97.97 ± 1.43% and 98.90 ± 0.38%, respec-
tively (Treatment-3 vs. Treatment-2, p < 0.01); meanwhile,
the success rate of 3D BRS reconstruction with high qual-
ity images at Baseline and Teatment-1, -2, -3 and -4 were
1.23%, 1.65%, 58.14%, 97.97% and 98.90%, respectively
(Treatment-3 vs. Treatment-2, p < 0.01). In conclusions,
reconstruction of 3D BRS images is technically feasible by
contrast-enhanced mCT and soaking time of contrast agent
for more than 2h is necessary for complete separation of
scaffold struts from the surrounding structures in the phan-
tom samples.
Keywords Bioresorbable scaffolds· Micro-computed
tomography· Contrast medium· Three-dimensional
reconstruction
Introduction
Bioresorbable scaffolds (BRSs), as the newest generation
of intracoronary stents, have shown an attractive pros-
pect due to their superiority over the conventional metal-
based stents [
1–4]. However, until BRSs can be safely
used for patients with complex lesions (tortuous, calcified
or bifurcated lesions), it is necessary to strictly examine
their maneuverability (deliverability, trackability), and
more importantly, mechanical properties (expandabil-
ity, durability, anti-fracture ability) [5, 6]. Hence, bench
testing is necessary while micro-computed tomography
(mCT) is deemed to be an essential imaging tool for visu-
alization of BRS configurations. However, the polymeric
Abstract There are no previous studies showing how
to visualize polymeric bioresorbable scaffolds (BRSs) by
micro-computed tomography (mCT). There are no previous
studies showing how to visualize polymeric bioresorbable
scaffolds (BRSs) by micro-computed tomography (mCT).
This study aimed to explore the feasibility of detecting
polymeric BRS with 3-dimensional reconstruction of BRS
images by contrast-enhanced mCT and to determine the
optimal imaging settings. BRSs, made of poly-L-lactic acid
(PLLA), were implanted in coronary bifurcation models.
Five treatments were conducted to examine an optimal con-
dition for imaging BRSs: Baseline treatment, samples were
filled with normal saline and scanned with mCT immedi-
ately; Treatment-1, -2, -3 and -4, samples were filled with
contrast medium and scanned with mCT immediately and
1, 2 and 3 h thereafter, corresponding to soaking time of
contrast medium of 0, 1, 2 and 3h. Compared to Baseline,
mCT scanning completely discriminate the scaffold struts
from the vascular lumen immediately after filling the sam-
ples with contrast agent but not from the vascular wall until
Electronic supplementary material The online version of this
article (doi:
10.1007/s10554-016-1049-z) contains supplementary
material, which is available to authorized users.
* Lianglong Chen
lianglongchenxh@126.com
1
Department ofCardiology, Fujian Medical University Union
Hospital, Fujian Institute ofCoronary Heart Disease, Fuzhou,
Fujian, People’sRepublicofChina
2
Department ofCardiology, The First Affiliated
Hospital ofZhengzhou University, Zhengzhou, Henan,
People’sRepublicofChina
3
Intensive Care Unit, The Second Affiliated Hospital
ofFujian Medical University, Quanzhou, Fujian,
People’sRepublicofChina
732 Int J Cardiovasc Imaging (2017) 33:731–737
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BRSs used currently are invisible directly by mCT. Up to
date, there are no adequate studies showing how to image
BRS by using mCT, particularly for the optimal condi-
tions for initial acquisition of the X-ray raw data and sub-
sequent reconstruction of 2- or 3-dimensional (2D/3D)
images albeit such images have been shown in several
previous invitro studies [7].
In this study, we explore the feasibility of imaging pol-
ymeric BRS with 3-dimensional reconstruction of BRS
images by contrast-enhanced mCT and to determine the
optimal imaging settings in bench testing.
Materials andmethods
Materials
Polymeric BRS (Neovas™, LePu Medical, Beijing,
China), a poly-L-lactic acid (PLLA) scaffold, was served
as testing scaffold and Ultravist (370mg/ml, iopromide,
Bayer Pharma AG), an iodinated medium, as the contrast
agent.
A coronary artery bifurcation model, made of polyvinyl
alcohol according to Murray’s law, was adopted for bench
testing, which has the distal bifurcation angle (DBA) of 60°
and branch diameter difference (BDD) of 0.50 mm. The
bifurcation model and BRS were incubated in a thermostat
water bath of 37 °Cduring scaffold deployment.
Experimental protocol
To determine an optimal condition for contrast-enhanced
mCT imaging, 15 phantom samples (scaffolds implanted
in the bifurcated model) received the following treatments:
Baseline or Control treatment, samples filled with normal
saline and scanned with mCT; Treatment-1, -2, -3 and -4,
samples filled with contrast medium and scanned with
mCT immediately and after 1, 2 and 3h, corresponding to
soaking time of contrast medium of 0, 1, 2 and 3h.
MCT scanning withraw data acquisition
CT scanning was performed using a mCT system (SkyScan
1176, Kontich, Belgium) to acquire a whole set of raw data
along the entire length of a phantom sample. The scanning
method and settings were: the sample was positioned on a
rotary plate with 360° rotation at the speed of 0.36°/s, with
a total of 800–1000 images recorded per sample. The X-ray
parameter was set at 65kV and 385μA, and scanning with
high spatial resolution of 18μm.
Analysis ofraw data
The acquired raw data consisted of three components:
phantom vascular wall (made of polyvinyl alcohol), vas-
cular lumen (filled with contrast agent) and scaffold struts
(rings and their connecting stems, made of PLLA). Usu-
ally, the phantom vascular wall was opacified partially
(grey) with different degree dependently on the soaking
time, vascular lumen opacified completely (bright) due to
filling with contrast agent, and scaffold struts not opacified
(dark) owing to PLLA resistance to contrast agent staining,
resulting in extremely low radiopacity.
For quantitative analysis, we randomly selected a 6-mm
segment from each phantom sample to measure the CT
attenuation of the phantom vascular wall, vascular lumen
and scaffold struts. By setting a cut-point of the CT value,
the scaffold struts could be extracted from the phantom vas-
cular wall and vascular lumen, and then the raw data com-
posing of scaffold struts only was digitally converted into
grey-scale images with DICOM format. Based on CT value
between 10 and 15 HU as cut-points, scaffold strut detect-
able rate (SDR, %), calculated by detectable struts/total
struts ×100, was optimal with almost no overlapping of CT
values among the three components of phantom samples.
3D reconstruction ofBRS
For offline 3D reconstruction, the grey-scale images (raw
data composed of the scaffold struts only) were inputted
into a computer installed with 3D reconstruction software
(SkyScan 1176, Kontich, Belgium), the 3D BRS images
could be automatically reconstructed with different quality.
The 3D image quality was graded according to the fol-
lowing criteria: (1) high quality, characterized by full
visualization of whole BRS configuration with complete
separation of all struts from surrounding structures; (2)
suboptimal quality, by partial visualization of BRS configu-
ration with missing some struts and incompletely separat-
ing some struts from surrounding structures; and (3) poor
quality, by incomplete visualization of BRS configuration
with missing many struts and incompletely separating
many struts from surrounding structures. The reconstruc-
tion of 3D BRS images with high, suboptimal and poor
quality was defined as success, partial success and failure,
respectively.
Statistical analysis
Data were analyzed with statistical software packages
(SSPS 22.0; SSPS, Chicago, IL). Data were expressed as
mean ± SD for continuous or frequency for categorical
variables. Analysis of variance (ANOVA) was conducted
for normally distributed continuous variables, followed
733Int J Cardiovasc Imaging (2017) 33:731–737
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by LSD test if significant; and Chi square or Fisher exact
probability test for categorical variables as appropriate. A P
value <0.05 was considered statistically significant.
Results
CT values anddetectable struts indifferent settings
As shown in Table1 and Fig. 1, the mean CT value was
highest in the vascular lumen and lowest in the scaffold
struts, which was constant independently on the soaking
time of contrast agent; whilst the mean CT value was in-
between in the vascular wall, which increased dependently
on the soaking time. As a result, separation of the scaffold
struts from the surrounding structures could be achieved as
the soaking time was ≥2h as in the treatment 3–4, favor-
ing distinguish of the scaffold struts from the vascular wall
and vascular lumen along the entire length of a phantom
sample.
Reconstruction of3D BRS images indifferent settings
The 3D BRS images with high quality could be obtained
as the raw data were good enough in quality as shown in
Fig.1 and Movie 1–5. As listed in Table2, mCT scanning
was unable to reconstruct 3D BRS images at Baseline and
in Treatment-1, and was able to partially reconstruct 3D
BRS images in Treatment-2, with only partial success rate
of 58.14%; while mCT scanning was able to completely
reconstruct 3D BRS images with similarly higher success
rate in Treatment-3 and -4.
Discussion
MCT, with capability of directly visualizing metal stents,
has been broadly adopted in assessment of stent perfor-
mance exvivo [8, 9]. However, most of BRSs currently
available were made of PLLA that is invisible directly
under mCT scanning. The present study was the first to
systemically examine how to visualize BRS implanted in
a bifurcated vascular phantom and then to reconstruct 3D
BRS images in bench testing, thus offering a basic tool
for exploring of BRS used in complex clinical scenarios
and for optimizing the interventional procedures. Our
major findings were: (a) soaking time of contrast agent
for more than 2 h is necessary for complete separation
of scaffold struts from the surrounding structures in the
phantom samples; (b) reconstruction of 3D BRS images
is technically feasible by contrast-enhanced mCT.
Optimal setting fordetecting struts andreconstructing
3D BRS images
The vascular bifurcation model used in the present study,
made of polyvinyl alcohol, is permeable to iodized con-
trast media and the infiltrating amount or rate is mainly
dependent on soaking time of contrast media, whereas
BRSs currently used clinically, made of PLLA, is imper-
meable iodized contrast media or resistant to contrast
media staining. Based on the rationale, it is possible to
distinguish the scaffold struts from the phantom vascular
wall and lumen with mCT scanning. Our study demon-
strated that soaking time for 2h or more is the best for
complete separation of the scaffold struts from surround-
ing structures under mCT scanning and for full recon-
struction of 3D BRS images with high quality as well.
In addition to the soaking time of the contrast agents,
sorts of contrast agents, materials of polymeric BRS or
vascular phantoms, and scanning settings including volt-
age/current, special and temporal resolutions may affect
acquisition of the raw data, thus significantly influencing
the optimal conditions for visualization of BRS struts and
subsequent reconstruction of 3D BRS images [10, 11].
Table 1 CT values and
detectable struts in different
contrast settings
Comparison of CT values among treatments: Treatment-1, -2, -3 and -4 vs. Baseline, *p < 0.01, respec-
tively; Treatment-3 and -4 vs. Treatment-2,
#
p < 0.01, respectively
Comparison of CT values among 3-components of the phantom sample: versus vascular wall,
∇
p < 001;
versus vascular lumen,
Δ
p < 001; versus vascular wall,
▲
p < 001
SDR scaffold detectable rate
CT value (HU) SDR (%)
Vascular wall Vascular lumen Scaffold struts
Baseline 3.06 ± 2.37 3.06 ± 2.19 3.13 ± 1.84 1.23 ± 0.31
Treatment-1 3.21 ± 2.24 231.73 ± 22.19*
,▲
3.12 ± 2.35 1.65 ± 0.26
Treatment-2 107.91 ± 16.27* 228.72 ± 25.92*
,▲
3.21 ± 2.39
∇,Δ
58.14 ± 12.84*
Treatment-3 171.29 ± 16.97*
#
232.15 ± 24.15*
,▲
3.13 ± 2.46
∇,Δ
97.97 ± 1.43*
,#
Treatment-4 178.21 ± 16.62*
#
233.92 ± 21.64*
,▲
3.12 ± 2.41
∇,Δ
98.90 ± 0.38*
,#
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Fig. 1 MCT raw data and reconstructed 3D images of BRS in differ-
ent settings. The cross-sectional images (raw data) of a phantom sam-
ple acquired by mCT scanning and corresponding 3D reconstructed
images of BRS in different treatments. At Baseline, mCT scanning
was unable to distinguish the three components of the phantom sam-
ple with only gold markers being detected. Regardless of complete
separation of the scaffold struts from the vascular lumen immediately
after filling the lumen with contrast agent, mCT scanning could not
clearly separate the struts from the vascular wall, failing to recon-
struct a 3D BRS image in Treatment-1; and could only separate par-
tial struts from the vascular wall, resulting in a suboptimal 3D BRS
image with some contamination of the vascular wall signal in Treat-
ment-2. Till to Treatment-3, mCT scanning was able to clearly sepa-
rate the struts from the vascular wall, enabling to completely recon-
struct 3D BRS images with high quality in Treatment-3 and -4
735Int J Cardiovasc Imaging (2017) 33:731–737
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Advantages of3D BRS images
The studies using the metal stent platforms suggesting that
the anatomic integrity of the vessel lumen plays a crucial
role in the maintenance of normal hemodynamics such
as local flow patterns and shear stresses. Accordingly, the
presence of any abnormal geometric configuration (i.e.,
oval lumen shape, malapposed struts, localized stent defor-
mation and so on) might be associated with turbulent flow
patterns and driving pressure loss, impaired shear-stress
pattern, abnormal platelet activation and even leading
to severe clinical events or complications [12–16]. Usu-
ally, polymeric BRSs are much thicker and more fragile in
Table 2 Quality of 3D reconstructed images in different contrast set-
tings
Comparison of image quality among different contrast settings: Vs.
Baseline, Treatment-1 and -2, *p < 0.01, respectively; vs. Treat-
ment-3,
#
p > 0.05
Image quality
Success (%) Partial success (%) Failure (%)
Baseline 1.23 0 98.77
Treatment-1 1.65 0 98.35
Treatment-2 0 58.14 41.86
Treatment-3 97.97* 2.03* 0
*
Treatment-4 98.90*
,#
1.10*
,#
0*
,#
Fig. 2 Display and application of 3D BRS images in bench testing.
After acquisition of high quality raw data of BRSs by using con-
trast-enhanced mCT, 3D BRS images could be easily reconstructed
and displaying in various formats: full 3D images (1st row A, F, K),
transverse cutting images viewed distally to proximally, or vice versa,
for inspection of MB ostium (2nd row B, G, L) and SB ostium (3rd
row C, H, M), coronal cutting images for examination of bifurcated
scaffold morphological features (e.g., scaffold expansion, coverage,
overlapping, distortion, rupture and so on) (4th row D, I, N), and strut
cross-sectional images (so called strut footprints) for accurately meas-
uring key parameters of bifurcated scaffold morphology (e.g., scaf-
fold luminal diameter and area, luminal symmetry, neocarina length
and so on) (5th row E, J, O). Also, in this case, BRSs (LePu Medi-
cal, Beijing, China) was used to exvivo emulate the three bifurcation
stenting techniques: CULOTTE (upper panels A, B, C, D, E), TAP
(middle panels F, G, H, I, J) and CRUSH (lower panels K, L, M, N,
O) with clearly showing the morphological characteristics of different
bifurcated stenting techniques by 3D reconstructed BRS images