1. Brian-Fred Fitzsimmons, MD2
eP -21: ASL Perfusion Imaging as a Surrogate Marker of Intracranial In-Stent Stenosis in the Setting of Stent Assisted Coiling; A Pilot Study.
Brian Graner, MD1
John Ulmer, MD1
Brian-Fred Fitzsimmons, MD2
Andrew Klein, MD1
Leighton Mark, MD1
1 Neuroradiology Section, Department of Diagnostic Radiology, Medical College of Wisconsin - Froedtert Hospital, Milwaukee, WI
2 Neurointerventional Division, Department of Neurology, Medical College of Wisconsin - Froedtert Hospital, Milwaukee, WI

2. Disclosures
The investigators have nothing to disclose.

3. Purpose
In-stent narrowing after stent assisted coiling of intracranial aneurysms has an incidence of approximately 5%, with reports ranging from 0% to 20%1-3.
DSA is the gold standard for assessment of the stent lumen
Patients are typically followed with noninvasive imaging (MRA)
MRA imaging of stented vessels is inherently limited secondary to metallic susceptibility artifact.
Loss of signal at both the periphery of the vessel and within the central lumen gives the appearance of “pseudo-narrowing.”
Figure 1A: 58 year old male status post stent assisted coiling of an 8 mm left MCA bifurcation aneurysm. Susceptibility artifact from the metallic stent artificially narrows the vessel lumen.

4. Purpose
2B) 09/24/2012
2C) 09/24/2012
2A) 10/04/2012
Figure 2: 72 year old male status post stent assisted coiling of a 5 mm mid-basilar aneurysm. Advance to next slide for zoomed in view.

5. Purpose
2B) 09/24/2012
2C) 09/24/2012
2A) 10/04/2012
Figure 2: 72 year old male status post stent assisted coiling of a 5 mm mid-basilar aneurysm. There is marked signal loss within the stented segment (arrowheads) when compared to signal within the ICAs and basilar tip on both time of flight MRA (figure 2B) and contrast enhanced MRA (figure 2C). DSA imaging confirms vessel patency (Figure 2A). Of note, residual filling of the aneurysm neck
beyond the stent wall is evident on all three modalities (arrows).

6. Purpose
Arterial spin labelling (ASL) perfusion imaging has been utilized in conjunction with MRA in patients who have undergone stent assisted coiling
Perfusion in the vascular territories downstream from the stented segment can theoretically serve as an indicator of flow limiting in-stent narrowing
While this practice has been anecdotally beneficial, longitudinal data is lacking
Figure 1A
Figure 1B: ASL perfusion imaging of the brain in the previously introduced 58 year old male status post stent assisted coiling of an 8 mm left MCA bifurcation aneurysm. No perfusion deficits are identified.

7. Purpose
The purpose of this study is to objectively assess the adequacy of ASL perfusion imaging as a reliable surrogate marker of flow limiting in-stent narrowing in patients who have undergone stent assisted coiling of an intracranial aneurysm.

8. Materials and Methods Subjects
Retrospective review of medical records (01/01/06 – 04/15/2015)
MRI radiology reports were searched using the following terms
“arterial spin labelling” OR “ASL”
“stent”
“coil”
Data
Demographic data and history collected
Age, gender
Vascular comorbidities, aneurysm risk factors
Clinical symptoms at the time of MRA follow-up
Procedural data collected
Date, details and results of the coiling procedures
Dates and results of follow-up MRA evaluations
Dates, details and results of follow-up DSA

9. Materials and Methods Imaging
Time of flight MRA, 3D contrast enhanced MRA and pseudocontinuous ASL perfusion imaging was completed using standard production sequences on both 1.5T and 3.0T clinical magnets
No additional sequences or exams were obtained for the purpose of this study
Analysis
ASL and MRA evidence for in-stent stenosis reported in the clinical interpretations was compared with conventional angiographic results
No retrospective imaging analysis was completed by the investigators for the purpose of this study
A time interval between the ASL/MRA and DSA evaluations of less than 12 months was considered relevant

10. Results Subjects (99 accession numbers) 29 accession numbers excluded
13 MRI and ASL/MRA accessions on same report
8 reports recommended ASL imaging on follow up
8 additional exclusions
70 accession numbers included
61 patients
42 of the 70 accession numbers had DSA follow-up (36 patients)
25 of the 42 identified ASL/MRA exams with DSA follow-up were performed within 12 months of the DSA procedure

11. Results Table I: Demographic and Aneurysm Data of 61 included patients
Male (%)
15 (25%)
Female (%)
46 (75%)
Mean Age (Std Dev)
59.3 (13.1)
Pts with Aneurysm Risk Factors (%)
55 (90%)
Multiple Aneurysms (%)
24 (39%)
Mean Aneurysm Size (Std Dev)
7.8mm (4.5)
Ruptured (%)
21 (34%)

12. Results In-Stent Narrowing (Table II)
In-stent narrowing was identified in 11 of the 36 patients with DSA follow up
Ranged from minimal narrowing to complete occlusion
4 cases were narrowed by greater than 50%
2 cases stented in the setting of rupture
2 cases had patent circle of Willis collaterals supplying the territory distal to the stent
In-stent narrowing resolved in 3 of the 11 cases
4 of the 11 cases of narrowing presented in the setting of rupture
3 of the 4 required stenting at presentation due to aneurysm anatomy
100% narrowing
30% narrowing
The 4th case was treated in a staged manner with coiling at presentation and stenting at a later date

13. Results
Table II: In-stent narrowing in 36 patients with DSA follow up (in order of % narrowing)
Rupture/ Elective
Stent placed at time of rupture
Aneurysm Size (mm)
Location
Stent
In-Stent Narrowing
Narrowing Identified
Configuration
Final DSA Follow Up
Treatment / Final Narrowing 1
Elective
N/A
6.9
Basilar tip
Neuroform 2 Neuroform 3
Severe
6 mos
2 stents, Y configuration, stenosis in P1 with patent Pcomm supplying P2
None 2
Ruptured
Yes
8.5
Pcomm origin
Enterprise
100%
2 weeks
ICA to mid M1 3 7
Neuroform 3
Immediately at placement
Mid Basilar to Pcomm, history of chronic occlusion of bilateral ICAs
One day
Patent stent with tiny non-occlusive thrombus distal to stent 4
7.3
ICA
80%
6mos
ICA at Opthalmic, Single Stent. Patient had 50% carotid bulb narrowing with patent circle of Willis.
5 yrs 4 mos
80% in-stent narrowing was treated with angioplasty and stenting (Wingspan) at 6mos with 20% residual stenosis. 20% narrowing stable at 5 yrs 4 mos. 5
MCA
40%
15 mos
Single stent, distal M1 to mid M2
16 mos
50%, appearance of neointimal hyperplaisia 6
Acomm
3.25 mos
Single stent, A1 to A2, narrowing in A1 portion of stent, patent Acomm
8.25 mos
35% narrowing A1 segment of stent, patent Acomm 8
35%
12 mos
Single stent, supraclinoid ICA
35 mos
No in-stent narrowing
6.5
Neuroform 3 Enterprise
30%
2 mos
2 stents, Y configuration, ICA to M1 and fetal Pcomm
9 mos 9
3 mos
Single Stent, ICA to M1 10 No 12
25%
10.75 mos
Single M1 stent, at early bifurcation
20.5 mos
25% narrowing 11
Minimal
16.75 mos
2 stents, Y configuration at bifurcation

14. Results Clinical Symptoms
5 studies associated with worrisome symptoms in 3 of 61 patients
1st patient (1 accession number): Aphasia, EEG showed discharges. ASL had no new deficits in stented territories; a remote infarct was evident. No DSA.
2nd patient (3 accession numbers): Left handed weakness after stent assisted coiling of paraclinoid right ICA aneurysm. History of antiphospholipid antibody syndrome and remote right MCA infarct. Two time periods:
1st time period, ASL negative, DSA showed patent stent.
2nd time period, ASL unremarkable, MRI showed acute/subacute focal infarcts, possibly embolic. No DSA performed.
3rd patient (1 accession number): Acute deterioration after stent assisted coiling of ruptured left Pcomm aneurysm. MRA, ASL and DSA were consistent with stent occlusion.

15. Results ASL and MRA performance versus DSA (Table III)
25 accessions had DSA within 12 months of the ASL/MRA study
ASL identified 3 of the 6 cases with DSA proven narrowing
3 false negative ASL exams:
1st and 2nd cases: normal perfusion secondary to circle of Willis collaterals distal to the in-stent narrowing (A1 segment stent and petrous/cavernous ICA stent)
3rd case: 35% in-stent narrowing at DSA
2 false positive ASL exams:
1st case: flow limiting atherosclerotic disease distal to the stent on DSA
2nd case: patient was taking clopidogrel for the 2 months between the ASL/MRA and DSA evaluations
MRA without ASL was inherently sensitive, although not specific, as narrowing versus pseudo-narrowing was discussed in 21 of 25 reports

16. Results ASL MRA ASL Adjusted True Positive 3 6 False Positive 2 15
Table III: ASL versus MRA in assessment of in-stent narrowing after stent assisted coiling of an intracranial aneurysm as determined by DSA. ASL results were adjusted for false negatives that would have no clinical implication (circle of Willis collaterals).
ASL
MRA
ASL Adjusted
True Positive 3 6
False Positive 2 15
True Negative 17 4 19
False Negative 1
Sensitivity
50.0%
100.0%
75.0%
Specificity
89.5%
21.1%
90.5%
Positive Predictive Value
60.0%
28.6%
Negative Predictive Value
85.0%
95.0%
Accuracy
80.0%
40.0%
88.0%

17. Results 05/13/2013 07/02/2013 09/13/2012 Figure 1B Figure 1A
Figure 1C: ASL True Negative. Coiling procedure and follow up DSA of previously introduced 58yo male status post stent assisted coiling of an 8 mm left MCA bifurcation aneurysm. Pseudonarrowing is evident on MRA, especially about the coil mass (arrows). ASL unremarkable.
No in-stent narrowing on follow up DSA

18. Results
02/17/2015
07/17/2015
04/14/2012
07/25/2014
Figure 3: ASL True Negative. 56 year old female status post partial coiling of a ruptured 5mm supraclinoid aneurysm on 04/14/2012 with subsequent pipeline stent placement on 07/25/2014. There is signal loss within the stented segment on MRA imaging (arrows). ASL
perfusion imaging is unremarkable. No in-stent narrowing on follow up DSA.

19. Results
03/13/2013
08/06/2010
02/01/2011
RT ICA
Figure 4: ASL False Negative. 62 year old male status post stent assisted coiling of a 7 mm basilar tip aneurysm. Follow up DSA shows near complete occlusion of right P1 stent (arrow). A prominent right Pcomm supplies the right PCA territory. MRA shows narrowing versus
pseudonarrowing (arrowhead). ASL perfusion imaging is unremarkable.

20. Results
11/27/2012
08/15/2013
05/18/2012
Figure 5: ASL True Positive. 74 year old female status post stent assisted coiling of a 7 mm left MCA bifurcation aneurysm. Follow up MRA shows narrowing versus pseudonarrowing (white arrows). Increased signal within the sulci of the left temporal lobe is suggestive of slow
flow (green arrows). DSA finds 40% narrowing within proximal stent (arrowhead).

21. Conclusion
Within the limitations of this retrospective clinical pilot study, traditional MRA for in-stent narrowing has a poor accuracy, largely due to artifact-induced pseudonarrowing resulting in multiple false positive exams.
When controlling for confounding false negative variables that would not have clinical implications, ASL accuracy and negative predictive value approach 90%.
The data suggests that downstream perfusion assessed by ASL in conjunction with MRA is a reasonable surrogate marker of clinically significant in-stent narrowing.

22. Bibliography
Fiorella D, Albuquerque FC, Woo H, et al. Neuroform In-stent Stenosis: Incidence, Natural History, and Treatment Strategies. Neurosurgery 2006;59:34-42.
Fiorella D, Albuquerque FC, Woo H, et al. Neuroform Stent Assisted Aneurysm Treatment: Evolving Treatment Strategies, Complications and Results of Long Term Follow-up. J NeuroIntervent Surg 2010:2:16-22.
McLaughlin N, McArthur DL, Martin NA. Use of Stent-Assisted Coil Embolization for the Treatment of Wide-necked Aneurysms: A Systematic Review. Surg Neurol Int 2013;4:43.