1. Arterial Spin Labeling MR Perfusion Acetazolamide Challenge for Assessing Cerebrovascular Reserve in Moya-Moya
Andrew Sung, David Shin, Eric Wong, Thomas Liu, Roland Lee, James Chen
University of California, San Diego Medical Center
Presentation Number: EE-07

2. Disclosures
None.

3. Cerebrovascular Reserve (CVR)
Measure of the ability for the brain to increase blood flow by autoregulatory vasodilation.
Evaluation of CVR is particularly useful for
Evaluating the risk of future ischemic events
Therapeutic interventions
Patient selection
Intervention planning

4. Acetazolamide (ACZ) Challenge
Acetazolamide (ACZ) is a vasodilator
Mechanism of action: carbonic anhydrase inhibitor, crosses blood-brain-barrier and causes cerebral acidosis  vasodilation  increased cerebral blood flow (CBF).
Systemic BP, HR, RR, arterial pH, arterial CO2, CMRO2 are unaffected.
By measuring pre and post ACZ CBF, can calculate the cerebrovascular reactivity:

5. Measuring Cerebral Blood Flow (CBF)
Imaging techniques:
Xe-CT
Perfusion CT (iodinated contrast)
MR perfusion
Contrast (Gd)– DSC
Non-contrast – ASL
PET (15O2, C15O2, H215O)
SPECT (Tc99m-HMPAO/ ECD)
Advantages of ASL
No radiation (vs. CT perfusion, Xe-CT, PET, SPECT)
No contrast (vs. CT perfusion, MR DSC perfusion)
Greater availability (vs. Xe- CT, PET)

6. ASL Cerebrovascular Reserve Protocol
Baseline ASL brain perfusion
Post-labeling delay (PLD): 2 sec
Labeling Duration (LD): 1.5 sec
Administration of acetazolamide 1g IV.
Wait minutes.
Post-acetazolamide ASL brain perfusion.

7. Case Report
29 year-old female with a history of Moya-Moya status-post left encephaloduroarteriosynangiosis (EDAS), presents with headaches, right-sided hemiparesis, and gait instability.

8. Imaging Findings
Magnetic resonance angiography (MRA) shows an occluded proximal left MCA (red arrow), with a left encephaloduroarteriosynangiosis (EDAS) (blue arrow).

9. Case Report
Unclear whether patient’s symptoms were from inadequate function of the EDAS versus other etiology.
Evaluation of cerebrovascular reserve was requested to assess need for further revascularization.

10. Results
ASL maps show appropriate response to acetazolamide administration with globally increased cerebral blood flow.
Subtraction images better demonstrate the relative difference in increased CBF following administration of acetazolamide.
Although there was relative less increase in CBF in the EDAS territory, no steal phenomenon was demonstrated.
Top row: CBF (Pre-ACZ)
Middle row: CBF (Post-ACZ)
Bottom row: Subtraction maps

11. Results
Absence of steal phenomenon suggests adequate function of the EDAS, and thus no further revascularization indicated.
Patient’s symptoms likely attributable to migraines.

12. Potential Pitfall
Transit Delay
Labeling Duration
ASL Signal
Post-labeling delay*
Time
Key assumption in ASL: post- labeling delay is longer than the longest physiologic transit time.
This allows the entire tagged bolus to reach the voxel before imaging.
* Conventionally, post-labeling delay accounts for the time after labeling and before imaging. For illustration purposes, post-labeling delay is shown to include the labeling time.

13. Potential Pitfall
Transit Delay
Labeling Duration
ASL Signal
Post-labeling delay
Time
Long transit delays, as seen in collateral flow states, may underestimate ASL estimated CBF if the post-labeling delay is not long enough.
This is due to the fact that the image is acquired before the entire tagged bolus reaches the voxel.

14. Post-Labeling Delay (PLD)
Transit Delay
Labeling Duration
ASL Signal
Post-labeling delay
Time
Thus, an appropriate PLD will allow for the entire tagged bolus to reach the target voxel before imaging.
Note, a PLD that is too long will allow the ASL signal to decay too much, resulting in decreased signal-to-noise (SNR).

15. Effect of Acetazolamide
Pre-ACZ
ASL Signal
Post-labeling delay
In long-transit states, such as in collateral flow, the pre-ACZ CBF measurement may be underestimated.
With acetazolamide administration, there is both a global increase in blood flow and decrease in transit delays.
This allows more accurate estimation of blood flow in the post- ACZ measurement.
Results in overestimation of the magnitude of delta-CBF, although, the direction of flow increase/decrease will remain the same.
Post-labeling delay
Post-ACZ

16. Choosing the PLD
Rule-of-thumb: set the PLD longer than the longest transit time.
2 seconds is adequate in most clinical patients.
Longer transit times (2-3 s) in elderly patients, collateral flow, stroke.
Troubleshooting: Curvilinear high signal (arterial transit artifact – ATA), reflects ASL tag within the arterial vasculature, and may indicate an inadequate PLD.
Arterial Transit Artifact (ATA) in Moya-Moya Patient
Zaharchuk G, et al. Stroke 2014.

17. Summary
ASL perfusion acetazolamide challenge can assess whole-brain cerebrovascular reactivity (CVR) without radiation or intravenous contrast.
This technique is particularly useful in any patients who may require multiple and frequent surveillance scans.
Particularly treated Moya-Moya

18. Summary ASL acetazolamide challenge benefits
Avoids repeated gadolinium contrast administration – a potential benefit given the current concern of linear gadolinium agents depositing in the brain with repeated administration.
Avoids repeated CT radiation dose and repeated iodinated contrast administration.
Has greater availability than Xe-CT or PET.
Can be easier to interpret - pre and post acetazolamide scans are performed in one scan session, allowing easy subtraction and interpretation. This is in contrast to the labor-intensive process of manual ROIs placement.

19. References
Zaharchuk G, Do HM, Marks MP, et al. Arterial Spin-labeling MRI can identify the presence and intensity of collateral perfusion in patients with Moyamoya disease. Stroke 2011; 42:
Yun TJ, Paeng JC, Sohn C, et al. Monitoring cerebrovascular reactivity through the use of arterial spin labeling in patients with Moyamoya Disease. Radiology 2016; 278(1):
Inoue Y, Tanaka Y, Hata H, et al. Arterial spin-labeling evaluation of cerebrovascular reactivity to acetazolamide in healthy subjects. AJNR Am J Neuroradiol 2014; 35:
Vagal AS, Leach JL, Fernandez-Ulloa F, et al. The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia. AJNR 2009; 30: