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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3592_Библиотеки_им_академика_М_И_Перельмана
.pdf
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
Figure 8.8. Example of the luminal area clustering result: selection of the cluster to analyze. The arrows
indicate the two candidates for analysis in this example.
significance level of
value of the pixel in the post-injection image
its corresponding value in the pre-injection image
of intensity in a pixel is significant if the null hypothesis for the pixel statistics is
= 0.005
. For this test, the null hypothesis is that the observed
Ci j(, )
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is not statistically different from
. We consider that a change
ij(, )
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
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rejected. Then, only pixels for which the null hypothesis is rejected are considered for
analysis. Finally, an enhancement image E is obtained by applying a threshold
to
e
the pixels of D:
Ei j
(, )
⎧
Di j Di j
(, ), if (, )
⎨
0, otherwise.
⎩
τ=⩾
e
(8.4)
8.2.2.3 Quantification of enhancement
The quantification of enhancement analysis is performed on a region of interest
(ROI) defined by the user in a frame of the sequence to analyze (figure 8.9).
Visualizations are created by mapping the differential image ROI D into the domain
of the original IVUS images F and overlaying them in a standard manner (e.g. using
color-mapping) so that enhancement may be viewed in its anatomical context.
Enhancement is quantified by computing the total enhancement area in pixels (Γ)
of those regions in the defined ROI:
Γ= Di j(, ).
∑
ij,
(8.5)
Additionally, the maximum and mean enhancement values corresponding to the
ROI are reported.
8.3 Results
In this section we present results for five cases acquired from human coronary
arteries using a solid-state array 20 MHz Volcano Therapeutics, Inc., Invision IVUS
system, and four cases acquired from rabbit aortas using a rotating 40 MHz catheter
with a Galaxy 2 Boston Scientific IVUS system. Recordings were performed as
follows. For the coronary artery of interest, an IVUS pullback was initially obtained
and the maximally stenotic point in the vessel located. The IVUS catheter was then
repositioned at this point and held steady over a matter of minutes. Baseline images
were acquired during a period of approx. 30 s, then a bolus injection of contrast was
administered through the guiding catheter (i.e. proximally to the imaging sensor)
Figure 8.9. Example of (a) a frame corresponding to a sequence to be analyzed and (b) the ROI selected for
enhancement analysis (i.e. plaque and media).
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and, finally, more images were acquired over 2 min. For all cases the contrast agent
used was Optison
TM
, a commercially available contrast agent whose constituent
microspheres are composed of octafluropropane gas surrounded by an albumin
shell. The mean bubble diameter is 3.7 μm with 95% of the bubbles being smaller
than 10 μm[31]; in comparison, the approximate diameter of a red blood cell is 8 μm
[8]. It is important to note that during the injection of the contrast agent, the lumen
region will depict a great echogenicity due to the passing of the microbubbles
(figure 8.10). However, it is common that the other structures of the vessel are no
longer visible during the injection since the majority of the ultrasound energy is
reflected by the microbubbles. Therefore, the proposed analysis is performed on the
frames corresponding to a selected period of time of 10 s before the first frame on
which the microbubbles can be detected in the lumen, and 10 s after the lumen is
visible again. The values for the Dice similarity threshold and the enhancement
threshold were empirically set to
= 0.9
d
and
, respectively. Table 8.1 lists
= 30
e
the resulting total enhancement areas for each case.
Figure 8.10. Example of a frame corresponding to the period during the injection of contrast agent.
Table 8.1. Quantitative enhancement-detection results. μ stands for maximal enhancement while Γ stands for
total enhancement area.
Case Id Subject IVUS frequency μ Γ
1 Human 20 MHz 179.2 2551
2 Human 20 MHz 90.2 989
3 Human 20 MHz 70.6 69
4 Human 20 MHz 43.2 30
5 Human 20 MHz 50.3 41
6 Rabbit 40 MHz 66.9 1007
7 Rabbit 40 MHz 123.5 488
8 Rabbit 40 MHz 188.2 1987
9 Rabbit 40 MHz 182.0 144
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8.3.1 Human cases
All human patients had indications for coronary percutaneous intervention and
intravascular ultrasound imaging. Written informed consent was obtained from all
patients and the study protocol was approved by the ethical committees of our
institutions.
Figure 8.11 depicts the results from case 1. Note that there exist multiple large
regions in the plaque and media/adventitia region, which depicts a large enhancement after the injection of contrast agent, suggesting the presence of extra-luminal
perfusion due to VV and VVP. In addition, there is some evidence of direct plaque/
microbubble interaction at the 12 o’clock region of the luminal border, where the
bubbles persist in a dense concentration. This could be evidence of a leaky plaque
(i.e. one with a disrupted cap).
Figure 8.12 depicts the results from case 2. In this case, the results suggest the
presence of extra-luminal perfusion in the media/adventitia region which may be an
indication of VV. Additionally, evidence of enhancement can be observed in a
Figure 8.11. Enhancement detection for case 1. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
Figure 8.12. Enhancement detection for case 2. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
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region of plaque near the lumen border (between 5 and 6 o’clock). While this may
indicate VVP, it also could be the result of endothelial adhesion of the contrast
agent.
Figures 8.13, 8.14 and 8.15 depict the results for cases 3, 4 and 5, respectively.
While there is some evidence of enhancement in certain regions we cannot ascertain
the presence of perfusion due to the small size and low enhancement value. Figures
8.14 and 8.15 depict the results for cases 4 and 5, respectively. In these cases, the
evidence of enhancement is not strong enough to assume the presence of perfusion.
8.3.2 Animal cases
New Zealand white male rabbits were fed an atherogenic diet for a period of three
months to develop atherosclerotic plaques. The plaques under investigation were
marked with surgical clips inserted externally by the surgeon on the aortic wall under
Figure 8.13. Enhancement detection for case 3. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
Figure 8.14. Enhancement detection for case 4. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
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Figure 8.15. Enhancement detection for case 5. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
Figure 8.16. Enhancement detection for case 6. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
fluoroscopic and IVUS guidance. CD31 was used in the histology as stain for
endothelial cells.
Figure 8.16 depicts the results for case 6. Note that there exists strong evidence of
enhancement in the media/adventitia region between 1 and 2 o’clock, and moderate
evidence of enhancement behind the plaque between 9 and 11 o’clock. Figure 8.17
depicts the histological slide corresponding to this case. As can be noted, ROI A
depicts a large vasculature in the adventitia region. Similarly, there exists evidence of
large perfusion in the adventitia on the ROI B, which appear to correlate with the
results of the proposed enhancement-detection method.
Figure 8.18 depicts the result for case 7. For this case, there exists some evidence
of enhancement in multiple sections of the media/adventitia region. By visual
comparison with the histology (figure 8.19), correlation between the enhancementdetection results and the histological evidence of extra-luminal perfusion can be
noted.
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Figure 8.17. Qualitative comparison of histology with the enhancement-detection of case 6. (a) Complete
vessel histology slide, (b) zoom on ROI A, (b) zoom on ROI B and (c) enhancement-detection result in the
polar B-mode image.
Figure 8.18. Enhancement detection for case 7. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
Figure 8.20 depicts the result for case 8. This case depicts a high density of
evidence of enhancement in the media/adventitia regions which correlates with the
high density of VV in the adventitia regions in the histology (figure 8.21). It is
important to note that there exists some evidence of enhancement in some regions
near the lumen which may be due to endothelial adhesion of the contrast agent.
Figure 8.22 depicts the results for case 9. In this case, the proposed enhancementdetection method did not find strong evidence of enhancement in any region. These
results also appear to correlate with the histological slide which depicts a poor
presence of VV (figure 8.23).
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Figure 8.19. Qualitative comparison of histology with the enhancement detection of case 7. (a) Complete
vessel histology slide, (b) zoom on ROI A, (b) zoom on ROI B and (c) enhancement-detection result in the
polar B-mode image.
Figure 8.20. Enhancement detection for case 8. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
8.4 Discussion
The significant changes in the IVUS signal after microbubble passage leave no doubt
as to its ability to show contrast enhancement. Compared with the other techniques
proposed for detecting VV on IVUS, the advantage of our method lies in the fact
that no special hardware or contrast agents are necessary (as in harmonic IVUS).
Instead, our method is able to detect perfusion within the ROI by using the data
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Figure 8.21. Qualitative comparison of histology with the enhancement detection of case 8. (a) Complete
vessel histology slide, (b) zoom on ROI A and (c) enhancement-detection result in the polar B-mode image.
Figure 8.22. Enhancement detection for case 9. (a) ROI enhancement before thresholding and (b) overlay of
detected thresholded enhancement in the mean post-injection image.
extracted from existing commercially available IVUS systems and contrast agents. It
is important to note, however, that due to the size of the microvasculature and its
elastic characteristics with respect to blood pressure, our method is most likely to
detect microvasculature with relatively large lumen areas or bundles of small-sized
microvessels. The primary limitation of our method is the requirement that we image
every area of interest twice: once before and once after the injection of contrast.
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Figure 8.23. Qualitative comparison of histology with the enhancement detection of case 9. (a) Complete
vessel histology slide and (b) enhancement-detection result in the polar B-mode image.
However, this limitation is necessitated by our desire to restrict ourselves to
currently available IVUS hardware and standard contrast agents. A second
limitation is that our method relies on accurate lumen segmentation on the frames
to be analyzed. However, this can be performed either manually or by one of the
many different methods proposed in the literature.
8.5 Conclusion
We have presented a method that enables in vivo imaging of extra-luminal perfusion
under IVUS using commercially available contrast agents. Current evidence and
knowledge suggest that this perfusion is related to the presence of VV microvessels
which, in turn, are a potential marker for plaque inflammation and consequent
vulnerability. As such, contrast-enhanced IVUS presents a promising imaging
approach to the assessment of plaque vulnerability.
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