1. Gastric Artery Embolization with X-ray-visible Embolic Beads and C-arm Cone Beam CT for Increased Accuracy
Clifford R. Weiss MD1, Paul DiCamillo MD PhD2, Weijie Beh3,Tza-Huei Wang PhD4, Hai-Quan Mao PhD5, Dara L. Kraitchman VMD PhD2,6
Radiology/Vascular and Interventional Radiology, The Johns Hopkins University School of Medicine
Radiology, The Johns Hopkins University School of Medicine
(3) Biomedical Engineering, The Johns Hopkins University School of Medicine
(4) Mechanical Engineering, The Johns Hopkins University Whiting School of Engineering
(5) Materials Science, The Johns Hopkins University Whiting School of Engineering
(6) Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine

2. What you’ve just learned!
No Data <10% %–14% %–19% %–24% %–29% ≥30%

3. What you’ve just learned!

4. What you’ve just learned!
Gastroenterology and Endoscopy News: April 2008 | v: 59:04

6. What you’ve just learned!
Paxton et al, SIR 2012

7. Weight change after bariatric embolization
(relative to untreated animals)
% wt gain
Week 4
Week 7
untreated
% wt loss
Bariatric embolization
Paxton et al, SIR 2012

8. Challenges Facing Embolic Therapy
Complicated Vascular Anatomy
Non-target embolization to spleen / liver / esophagus / pancreas / intestine or “non-fundal” portions of stomach

9. Challenges Facing Embolic Therapy

10. Challenges Facing Embolic Therapy+

11. Challenges Facing Embolic Therapy
BETTER SEE WHERE
WE’RE GOING
KNOW WHERE WE’VE BEEN

12. CT using Conventional Angiography
C-arm Cone Beam CT
(CBCT)
Flat panel
angiography
8 s acquisition
Methodology for c-arm CT using flat-panel X-rayl fluoroscopic system

13. Prototype Microfluidic Device
Check Valve
Prototype Microfluidic Device
Barium-sulfate
Alginate
Oleic Acid
Palginate>Pvalve>Poil
IPA/ Ca Cl2
IPA/Ca Cl2
Ca2+

14. X-Ray Visible Embolic Beads (XEB) Microfluidic Device
Size determined by nozzle size & flow rate
Pressurized system prevents clogging of nozzles at high generation rates
Scale up by parallelization of device allows production of microbeads at rates of ~1 kHz.

15. XEB Generation
Microbead production is performed at a slower rate to show the production of beads within the microfluidic device. An individual bead (arrow) is shown in successful frames every 5 ms moving down the channel.

16. SEM of XEBs
Note uniformity of the microbeads based of scanning electron micrographs

17. Fundal Anatomy and Arterial Map
Here is a diagram of the arterial supply to the fundus
We will target the three vessels that supply the fundus
For the purposes of our talk, we will call the Fundal, Left Gastric and Right Gastric
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Colon / SMA  enlarge to see vessel  fundus with shading L 0.9, T 1.4, R 1.6, B 1.0, H3.5 H
28 point or larger 1,2,3
Pop – up boxes with 3 branches
We will target its complete supply – the three locations noted here:

18. Beads: Fabrication
Custom made, barium sulfate containing, highly uniform alginate beads (~50 μm) served as the embolic agent in this study.
Made with microfluidic devices with pressure controlled flow rates for uniform production
The bead fabrication and properties were discussed in the previous lecture By Dr. Kraitchman
They are made on microfluidic devices with pressure controlled flow rates for uniform production
Importantly, they are fluoroscopically and CT visible, they are uniform, and they are small (50um)
No Need for endogenous contrast during delivery

19. Overall Approach Pre-embolization DSA CBCT Celiac DSA
C-Arm Cone Beam CT (CBCT):
DynaCT: AXIOM Artis dFA (Siemens Healthcare, Forchheim, Germany)
8s DSA or DR,
210° rotation,
0.5°/ step,
contrast 25% iohexal
Pre-embolization
DSA CBCT
Celiac DSA
Directly Visualized Embo
Repeat for each site
Post-embolization
CBCT DSA
We access the celiac axis
At each of the three sites we do the following
pre embolization digial subtraction angiography
c-arm cone beam CT
this is when you have the flat panel of the CT swing around the patient and take a rotational angiogram
then you can reconstruct it into a CT / for cross sectional imaging in the flouro suite
next, under direct visualization, we embolize
finally, we assess success with DSA and c-arm cone beam CT
we repeat for each site
at the end of the experiment, we sacrifice the animal to perform histopathological evaluation of the procedure
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for gross pathology and histology
** label CBCT / DSA
On swine
We access the celiac axis and image with DSA
For each target site, we image before and after with DSA / Cone Beam CT
And embolize under direct fluoro visualization
Three 35kg Yorkshire Pigs
5F SOS selective catheter access to celiac axis (femoral)
Digital Subtraction Angiography (DSA) of celiac axis
For each targeted location:
Select fundal vessel via Renegade Hi-Flow w fathom wire
Pre embolization imaging (DSA / DynaCT)
Cone Beam CT: DynaCT: AXIOM Artis dFA
8s DSA or DR, 210° rotation, 0.5°/ step, contrast 25% Omnipaque
(Siemens Healthcare, Forchheim, Germany)
Bead Injection under direct fluro observation
Post embolization imaging (DSA / Dyna CT)
At end of session
Black tissue dye staining from celiac trunk
Sacrifice, gross pathology, histology
Pathology/Histology

20. Celiac Axis GACE 1, Series 3
Starting off, we perform a DSA on the celiac axis
Note the angiogram corresponds to the diagram
Here are the three target branches
FUNDAL
LEFT GASTRIC
RIGHT GASTRIC
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Color three branches, red yellow green
GACE 1, Series 3

21. Approach to Site 1: Avoiding Reflux to Spleen
We are approaching the target site 1 – (what we are calling) the fundal artery
SOS selective catheter, Renegade high Flow catheter
In this panel, there is contrast to target and also to spleen
Advancing, we position in site 1. We will have to control delivery rate to avoid backflow to spleen
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Now both 26 frames
Series 5: 6-36 (31 frames)
Series 6: 7-29 (23 frames)

22. “Fundal Branch” Embolization
Pre-embolization
Post-embolization
Pre and Post embolization at the fundal artery site 1
Here is the SOS selective catheter, Renegade high Flow catheter
In this panel, you see the blushing of the target tissue
After embolization, the blush is gone and the vessels are truncated
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Now series 6 and 16, each 26 frames
Series 6: 7-29 (23 frames)
Series 15: 5-42 (38 frames)

23. Beads are Visible During Delivery
As the beads have endogenous contrast, they can be visualized during delivery
Here is the tip of the renegade high flow catheter
Site 1 – beads can be visulaized during delivery
The are visualized with only their endogenous contrast
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Note there is no contrast in injection – only opacity of beads is noted

24. Site 1: C-arm Cone Beam CT Pre Contrast Post
Sagittal Coronal Axial
With the C-arm cone beam CT we get more detailed information about the case
Here are: axial, coronal, sagital sections
axial
This is the stomach, the spleen
Coronal
saggital
This is the stomach
On this plan: Pre-embolization – we can visualize fundus
On this panel: we inject contrast to verify we are in the arterial supply to the fundal tissue
On this panel: we can see where the beads have been delvered  only to the fundus tissue, not the spleen or other organs
We verify targeting of fundus 3 dimensions in second panel
In the right panel, image of beads post-embolization
Use 2nd run for 25% contrast  update images
Change DYNA  to CB CT
GACE001_S19_DYNACT_POST_EMBO_1_AXIALGRAYSCALE1
(want 3rd one that is embo site three in three planes)
GACE 1, Series 7,19, 29

25. “Fundal Branch” CBCT Pre Contrast Post
Sagittal Coronal Axial
With the C-arm cone beam CT we get more detailed information about the case
Here are: axial, coronal, sagital sections
axial
This is the stomach, the spleen
Coronal
saggital
This is the stomach
On this plan: Pre-embolization – we can visualize fundus
On this panel: we inject contrast to verify we are in the arterial supply to the fundal tissue
On this panel: we can see where the beads have been delvered  only to the fundus tissue, not the spleen or other organs
We verify targeting of fundus 3 dimensions in second panel
In the right panel, image of beads post-embolization
Use 2nd run for 25% contrast  update images
Change DYNA  to CB CT
GACE001_S19_DYNACT_POST_EMBO_1_AXIALGRAYSCALE1
(want 3rd one that is embo site three in three planes)
GACE 1, Series 7,19, 29

26. “Fundal Branch” CBCT Post Embolization
Scrolling through the CBCT gives an idea of the extent of bead distribution from site 1
This is a powerful intra-procedural confirmation
Note the beads in site one, and no beads in other tissues
Site one, image of beads postembolization

27. Site 1: Bead are Visible During Delivery
Another image of the beads being delivered
Here is the SOS Selective Catheter
Here is the renegade high flow catheter
Here are the beads being injected
You can see the endogenous contrast of the beads
Site 1 – beads can be visulaized during delivery
The are visualized with only their endogenous contrast
Site one: Still image of beads during injection: (Stacked image)
DSA with beads at 3 frames per second
GACE 1, Series 11

28. Left Gastric? GACE 1, Series 20, 21 Now we move to site two
We choose the fundal vessel with fathom wire and advance renegade high flow catheter
GACE 1, Series 20, 21

29. Site 2: C-Arm Cone Beam CT
We take a look with c-arm cone beam CT prior to embolization – this is a rotational angiogram
We want to verify the perfusion pattern of tissue downstream of the catheter
8 s C-arm CBCT, 25% iohexal at 1cc/sec

30. Right Gastric Embolization
Pre Embolization
Post Embolization
We moved on to site three – the Right Gastric
We are approaching the target site 3 – (what we are calling) the right gastric
SOS selective catheter, Renegade high Flow catheter
In this panel, you see the blushing of the target tissue
After embolization, the blush is gone and the vessels are truncated
------
Advancing, we position in site 1. We will have to control delivery rate to avoid backflow to spleen
Moving to Site three,
Here are DSAsof the pre-and post DSA
Pre: 22
post: 28

31. Embolization at Site 3 Post Embolization Pre Embolization
Still images from site 3 – the right gastric
Here is the Renegade high Flow
In this panel, you see the blushing of the target tissue
After embolization, the blush is gone and the vessels are truncated
------
Moving to Site three,
Here are still captures of the pre-and post DSA
DSA with 25% iohexal at 6 frames per second

32. Right Gastric CBCT Pre Contrast Post
Sagittal Coronal Axial
With the C-arm cone beam CT we get more detailed information about the case
Here are: axial, coronal, sagital sections
Axial
This is the stomach, the spleen,
beads delivered to site 1
Coronal
Saggital
This is the stomach,
On this plan: Pre-embolization – we can visualize
fundus and ,
On this panel: we inject contrast to verify we are in the arterial supply to the fundal tissue
On this panel: we can see where the beads have been delivered 
beads delivered to site 1,
new beads delivered to site 3
note that the beads have only been delivered to the fundus tissue, not the spleen or other organs,
With C-arm cone beam CT,
Top to bottom – axial, coronal, sagital
On the left – pre embolization – you can see the beads from embolization at site 1
In the center panel, we verify location in 3D with contrast
In this panel, we see the beads post-embo

33. Procedure Summary Pre Post “FB” Post RG Sagittal Coronal Axial
Review of work at site 1 and site 3, C-arm cone beam CT
Here are: axial, coronal, sagital sections
axial
This is the stomach, the spleen
Coronal
saggital
This is the stomach
On this panel: Pre-embolization – we can visualize fundus
On this panel: After treating site 1:
we can visualize fundus
beads delivered to site 1,
note there are no beads in other tissues
On this panel: After treating site 1 and 3:
beads delivered to site 3,
On this panel: we can see where the beads have been delvered 
only to the fundus tissue, not the spleen or other organs,
new beads delivered to site 3
Trap in capillary bed contrast from previous DSA
Will wash out as seen in site one
Not in this study  point of care / investigate further to see how the beads persist over time and their contrast persist
Capitol P – pre and post  dyna ct to cbct
Loop of 3 d scroll
Now we move to site two
We choose the fundal vessel with fathom wire and advance renegade high flow
N= 3 swine

34. CBCT Post Embolization
Scrolling through the CT acquisition, we can see the extent of embolization in sites 1 and 3
On this panel: After treating site 1 and 3:
we can visualize fundus
beads delivered to site 1,
beads delivered to site 3,
note there are no beads in other tissues
This is a powerful intra-procedural confirmation
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Scrolling through the CBCT gives an idea of the extent of bead distribution from site 1

35. Return to Site #2 to Find Left Gastric
Now on our way out, we stop by site 2,
Select the left gastric with the renegade high flow
And confirm
Went to site to access. Did not inject beads----
Now we move to site two
We choose the fundal vessel with fathom wire and advance renegade high flow
Windowed for contrast (bead loss)
Possible to access  but demonstrate possible

36. Gross Pathology
At the end of the procedure, we inject a histological stain - essential black dye – to mark the areas still perfused
We sacrifice the animal and look at the gross pathology
The pale areas have been embolized.
see we hit the whole fundus
The dark areas still are perfused
The entire fundus has been covered
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the areas of preserved perfusion

37. Fundus 10x 2x Moving to histology….
Here is an H&E of the gastric fundus at low power (2X)
For orientation: mucosa, submucosa, muscularis
The arrows point to beads in arteries in the submucousa
Moving to 10X, the beads are visible – a single bead in each vessel
Low, Arrows, beads,
Histological Images
See the 50 micron beads reach deep into the vascularute – lodging in the submucosa
Another image of the fundus
Beads are here
Another image, this time of the cardia
No beads
10x 2x

38. Body 2x
Here is an H&E of the body of the stomach at low power (2X) – we did not target that area
For orientation: mucosa, submucosa, muscularis
The arrows point to beads in arteries in the submucousa
Moving to 10X, there are no beads evident in the vessels
Low, Arrows, beads,
Histological Images
See the 50 micron beads reach deep into the vascularute – lodging in the submucosa
Another image of the fundus
Beads are here
Another image, this time of the cardia
No beads
10x

39. Conclusions
Combination of XEB and CBCT allows the interventional radiologist to:
Better see where they are going
See where they have been
Allows for complete fundal embolization
Better assessment of treatment successes and failures
Should allow for “long term”
Allow Interventional Radiologist to determine if re-embolization is needed
In conclusion
For bariatric embolization, to target the arterial supply to a specific part of the stomach, we used two methods to facilitate the work
Uniform, 50 micron (small), X-ray visible beads
so you can see the beads during delivery to modulate injection rate, reduce back flow
so you know where you’ve been when making choosing subsequent targets and making future injections
C-arm Cone Beam CT
so you can visualize the soft tissues
visualize the perfusion to the tissue of interest
see the beads afterwards in 3 dimension to be confident of the therapy
TOGETHER THEY ALLOW FOR A SAFE AND COMPLETE EMBOLIZATION OF THE STOMACH
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allow visualization during and after delivery – so you know where you’ve been
To know downstream targets, and get 3D confirmation of progress and remaining targts

40. Broader Implications
Not only promising for improving Bariatric Arterial Embolization (BAE/BE)
Current embolic therapy is growing market:
Hepatocellular Carcinoma
Other Tumors
Uterine Fibroids
Bronchial Artery Embolization