1. Moya Moya on MRI and MRA eEdE#: eEdE-183 Control #: 2500
Steven Sogge, MD
Krish Thamburaj, MD

2. Financial Disclosures
We do not have any financial disclosures.

3. Objectives Review the classification and pathophysiology of Moya Moya
Review the various neuroimaging features of Moya Moya disease on MRI and MRA

4. Well known causes of Moya Moya syndrome
Definition
Puff of smoke
Progressive stenosis of the terminal internal carotid bifurcation including terminal ICA and the proximal segments of ACA and MCA in association with development of dilated perforating arteries that function as collateral pathways. The Japanese term ‘Moya Moya’ is derived from the resemblance of the basal collaterals to puff of smoke on cerebral angiography.
Guidelines published by the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) in 1997 defined the disease as:
Moya Moya Disease: Bilateral lesions with no known etiology
Probable Moya Moya: Unilateral lesion
Moya Moya syndrome: Bilateral lesions occurring in the background of an underlying lesion
Well known causes of Moya Moya syndrome
Atherosclerosis (Probably the most common secondary cause)
Sickle cell disease
Down’s syndrome
Neurofibromatosis
Autoimmune disease
Meningitis
Head trauma
Irradiation to the head

5. Epidemiology
Observed throughout the world. High incidence in East Asia. In Japan, the annual prevalence and incidence have been estimated at 3·16 and 0·35 per , respectively.
Incidence from western parts of USA 0.086/100,000. Incidence- rate ratios reported in Asian Americans 4.6, Blacks 2.2, and Hispanics 0.5, as compared with Whites.
F: M = 1.8
Age: Bimodal distribution, primary peak at age 5 with smaller peak at age 40.

6. Pathophysiology Not completely understood
Stenosis starts at distal ICA. May start in proximal MCA or ACA before progressing to terminal ICA.
Pathology of affected vessel demonstrates smooth muscle proliferation and intraluminal thrombi. Fragmented undulated internal elastic lamina and thin media are evident.
Caspase-3-dependent apoptosis might be associated with these histopathological changes.
Moya Moya vessels also demonstrate similar changes in vessel wall; fragility of vessel wall may result in microaneurysm formation. These histopathological changes might be closely associated with the onset of ischemic and hemorrhagic stroke.
(Hematoxylin & eosin) of right terminal ICA shows hyperproliferation (black arrow) of the vessel-wall components and abundant intraluminal thrombi (blue arrow), leading to narrowing and occlusion of the lumen. Scott RM et al., NEJM 2009;360:1226

7. Clinical presentation
Trasient ischemic attacks (TIA) and ischemic infarcts typically in younger children. Areas affected tends to be in the territory of the ICA, particularly in the frontal lobe. Repeated insults can lead to impairment of higher order functions later in life.
Hyperventilation will induce ischemic attacks secondary to decreased PaCO2 which leads to arterial vasoconstriction.
Intracranial hemorrhage occurs more commonly in older individuals, those typically occurring around the second peak of incidence. There are two causes of bleed; the first is ruptured of dilated fragile moya moya vessels or rupture of saccular aneurysms that occur in the setting of the disease.
Headache
Epilepsy
Involuntary movements

8. Diagnostic criteria and classification
Historically, cerebral angiography is the gold standard.
Cerebral angiography is less than ideal in the primary population affected by Moya Moya due to ionizing radiation exposure.
Per guidelines from the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moya Moya Disease), cerebral angiography is not mandatory if MRI and MRA demonstrate:
Stenosis or occlusion at the end of the ICA or at the proximal part of the ACAs and MCAs on MRA, and an
Abnormal vascular network seen in the basal ganglia with MRA.
The new criteria of the Research Committee for Diagnosis of Moyamoya Disease recommend MRA with a 1·5T machine, and MRA scans with 0·5T or 1·0T machines are not recommended
Stenosis or occlusion of the terminal part of the ICA (the C1–C2 portion) and the proximal part of the ACAs and MCAs bilaterally.
Stenosis or occlusion of the proximal part of the posterior cerebral artery also affects about 25% of patients with Moya Moya disease.

9. Angiographic Classification of Moya Moya (according to Suzuki and Takaku)
Stage
Carotid terminus (CT)
Moya Moya collaterals I
Narrowed
None II
Narrowed CT and dilated ACA & MCA
Initiation
III
Increasing stenosis of CT and narrowed ACA & MCA
Intensification IV
Occlusion in ICA and tenuous ACA & MCA
Minimization V
Occlusion of ICA, ACA and MCA
Reduction VI
Vanished ICA with ECA supply to brain
Disappearance
DSA demonstrates Stage II Moya Moya in bilateral carotid terminus with unaffected posterior circulation. Note the severe stenosis in terminal ICA, carotid bifurcation and bilateral A1 and M1 segments. Posterior circulation is less involved in up to 25% of cases.

10. Parenchymal changes Ischemic stroke presentation Infarcts:
FLAIR
DWI
ADC
MRA
Ischemic stroke presentation
Infarcts:
Ischemic infarcts occur in deep gray matter, periventricular white matter, cortical areas particularly in frontal lobes and watershed areas.
Acute infarcts are shown best on DWI
Subacute infarct demonstrate enhancement
Chronic infarct demonstrated by encephalomalacia and gliosis
Pathophysiology of ischemia
In children, hyperventilation during crying may result in vasoconstriction and ischemic events. Exertion of induction of anesthesia may also precipitate ischemic events.
Ultimately the brain undergoes atrophic changes.
Moya Moya disease with acute infarct in the right temporal lobe (arrow).
FLAIR
Postgad T1
Moya Moya patient with enhancing subacute ischemic infarct in the corpus callosum

11. Parenchymal changes FLAIR FLAIR T1 FLAIR T1
Serial MRIs show progression of infarcts, initially presenting as unilateral disease on left and progressing to bilateral disease. Again note the vulnerability of frontal lobes.
Deep gray matter infarcts are well known in Moya Moya. Note the chronic infarcts in left basal ganglia (arrow)
Periventricular white matter (PVWM) is another area prone to develop infarcts in Moya Moya. Note the chronic infarcts in bilateral PVWM (arrows)
Superficial watershed infarcts acute and chronic stages on DWI, T1 and FLAIR sequence along the right centrum semiovale (arrows)
DWI T1
FLAIR

12. Parenchymal changes Posterior circulation infarct
FLAIR
MRA
Posterior circulation involvement is less common in Moya Moya. It may be seen in up to 25% of cases. Note the chronic infarcts in bilateral posterior cerebral artery territory on FLAIR (arrows). Also, note on MRA, the lack of flow signals in bilateral posterior cerebral arteries (arrows).

13. Intracranial hemorrhage
T2*GRE
MRA
Hemorrhagic stroke presentation
More common in adults
Pathophysiology: Fragile vessel wall and microaneurysms probably predispose pattients to intracerebral hemorrhage and intraventricular hemorrhage. Hemorrhage in the basal ganglia is well known to occur in Moya Moya. Hemodynamic factors may occasionally result in development of aneurysms at the circle of Willis and episodes of subarachnoid hemorrhage.
Isolated intraventricular hemorrhage. Demonstrates hyperintense T1 signals, susceptibility on T2* GRE from intracellular methemoglobin (arrows). Occlusion of bilateral carotid terminus evident on MRA (arrows).
Intracerebral hemorrhage: Typically occur in basal ganglia.
Intraventricular hemorrhage: Isolated IVH is well known to occur in Moya Moya, probably due to rupture of fragile hypertrophied choroid vessels.
Subarachnoid hemorrhage: Uncommon; May result in aneurysmal pattern from ruptured aneurysm developing in response to hemodynamic factors. Maya Moya may result in isolated convexity sulcal hemorrhage.
Cerebral microbleeds: Some studies report higher incidence of cerebral microbeleeds in Moya Moya. They tend to be located near the periventricular white matter.
SWI
Cerebral microbleed on SWI in left periventricular white matter (arrows).

14. Ivy sign
Seen on FLAIR sequence. The sulci appear hyperintense. Can be unilateral or bilateral.
Ivy sign is thought to indicate leptomeningeal collaterals. Slow flow in cortical vessels also cause sulcal hyperintensity.
Differential for sulcal hyperintensity on FLAIR:
O2 inhalation
Acute subarachnoid hemorrhage
Meningitis of all causes
CSF flow artefacts
FLAIR
FLAIR
Postgad T1
Postgad T1
FLAIR
Sulcal hyperintensity (Ivy sign) evident on FLAIR especially on the left side (arrows)
Bilateral Ivy sign evident on FLAIR. Enhancing vessels are seen in postcontrast T1 corresponding to the Ivy sign findings (arrows)
Ivy sign on FLAIR from slow flow in a vessel right posterior temporal region (arrow). Enhancing vessels evident on postcontrast T1 (arrows). This was the only finding in a child presenting with an episode of syncope which led to the diagnosis of Moya Moya

15. T2 T1
Collaterals on MRI
Collateral pathways: Based on catheter angiography, classified as
Basal moyamoya – From lenticulo-striate artery and the thalamo-perforating artery.
Choroidal & Pericallosal
Ethmoidal moyamoya – From anterior and posterior ethmoidal arteries
Vault moyamoya - from dural arteries to pial arteries - it is commonly observed in patients with advanced disease.
Effective bypass surgery can result in disappearance or regression of moyamoya vessels, as they are no longer required to function as collateral pathways.
Basal collateral seen as tiny multiple flow voids on T2 against the bright CSF (arrow). Note the diminished caliber of MCAs
Collaterals seen as flow voids on T1 in bilateral basal ganglia and thalamus (arrows) PD
Postcontrast T1
Basal collateral seen appear as flow voids as well as prominence of perivascular space on Proton density weighted image (arrow). Note the distinct enhancing perforators on postgad T1 (arrows).

16. SWI in Moya Moya SWI can demonstrate:
All forms of hemorrhagic stroke at greater sensitivity than T2*GRE
Depending on the territory involved, ischemia leads increased oxygen extraction and higher concentration of deoxyhemoglobin in the cortical and perimedullary veins. These veins demonstrate more susceptibility signals on SWI in the affected side.
mIP image of SWI
mIP image of SWI
MRA
Brush sign seen in Moya Moya: Prominence of perimedullary veins evident on the left side (arrows). Also, note the prominence of cortical veins in the left MCA territory.
Prominent cortical veins from increased deoxyhemoglobin in right MCA and bilateral ACA territory (arrows). MRA shows patency of LMCA (arrow). Right supraclinoid ICA, RMCA and bilateral ACAs are affected.

17. MRA in Moya Moya
Technique: Time of flight is the most commonly used technique. Lack of ionizing radiation and lack of IV contrast are major advantages.
TOF MRA may overestimate stenosis as occlusion.
MRA can also can be used to identify Moya Moya collaterals.
MRA scores correlated well with the six-stage classification on cerebral angiography, with a high sensitivity and specificity.
Can be used to monitor the disease progression as well as post surgical changes.
In accordance with the guidelines of the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moya Moya Disease), cerebral angiography is not mandatory if MRI and MRA show all of the following findings:
Stenosis or occlusion at the end of the ICA or at the proximal part of the ACAs and MCAs on MRA, and an
Abnormal vascular network seen in the basal ganglia with MRA.
The new criteria of the Research Committee for Diagnosis of Moya Moya Disease recommend MRA with a 1.5T machine, and MRA scans with 0.5T or 1.0T machines are not recommended.

18. Stage 3/4 MRA MRA MRA Selective RICA DSA Selective LICA DSA VA DSA
MRA demonstrates severe stenosis of bilateral carotid terminus (yellow arrows); Note the basal collaterals near the bilateral carotid bifurcation (red arrow). The posterior circulation is also involved (blue arrow).
DSA demonstrates findings similar to MRA. Suzuki stage 3 to 4 bilaterally with prominent collaterals. Note the involvement of bilateral posterior cerebral arteries on vertebral DSA (yellow arrows).

19. Stage 4/5 MRA MRA MRA Selective RICA DSA Selective LICA DSA VA DSA
MRA demonstrates severe stenosis of right carotid terminus (yellow arrow); Left carotid terminus is occluded (red arrow). Note the intact posterior circulation (blue arrow).
DSA demonstrates findings similar to MRA. Suzuki stage approximately corresponds to 4 on the right side and 5 on the left side

20. Collaterals on MRA
MRA can reliably demonstrate various types of collaterals in Moya Moya
Raw data TOF MRA
Raw data TOF MRA
MIP image of TOF MRA
Flow signals from in collateral from posterior cerebral arteries (arrows).
Note the tiny flow signals from collateral in the right sylvian fissure and right basal ganglia (arrows). Note the distinct enhancing perforators on postgad T1 (arrows). Note the stenosis/occlusion in right carotid terminus in MIP image (arrow)
MIP image of TOF MRA
Raw data TOF MRA
MIP image of TOF MRA
Collateral evident in bilateral medial thalamus as well as in the quadrigeminal cistern (arrows).
Enlarged left anterior choroidal artery (arrows).

21. Treatment options
Goal of treatment is to prevent future ischemic strokes.
Revascularization options:
Direct: Involves anastomosis of a branch of the internal carotid artery either MCA or ACA with a branch of the external carotid artery to bypass the ICA stenosis.
Indirect: Vascularized tissue supplied by external carotid artery is placed contact with the brain to promote ingrowth of blood vessels.
Types of indirect surgery
Encephalogaleosynangiosis
Encephaloduroarteriosynangiosis (STA-dura)
Encephalomyoduroarteriosynangiosis (Temporal muscle-dura)
Multiple burr hole surgery
From:
In this surgery the superficial temporal artery (STA), which is a branch of the external carotid artery, is anastomosed to the cortical conducting branches of the middle cerebral artery or cortical conducting branches of ICA
From:
Encephaloduroarteriosynangiosis

22. MRA and post surgical changes
Encephaloduroarteriosynangiosis (EDAS): - Enlargement of the superficial temporal artery (STA) and middle meningeal artery (MMA) can be observed; Approximately 3 months later, well developed collaterals can be seen on MRA.
EDAS has a high success rate in pediatric cases. In adults, 40-50% of cases may not develop adequate collaterals.
STA-MCA bypass: Patency can be assessed on MRA. Aneurysm may develop rarely at the site of anastomosis. MRA can help identify the complications.
Post treatment changes:
• Moya Moya vessels start regressing 1 month after combined bypass surgery. STA and MMA increase their caliber in 3 months after surgery. Stenotic change in the carotid terminations quickly progresses after surgery. There is a reciprocal relation between neovascularization and the regression of moyamoya vessels.

23. MRA appearance of Encephaloduroarteriosynangiosis
DSA frontal view
DSA lateral view
Right carotid DSA demonstrates right encephaloduroarteriosynangiosis. Note the anastomotic site at the level of the dura (arrow) in the frontal view. In the lateral view, hypertrophied parietal branch of STA is seen (yellow arrow). Collaterals opacifying the cortical branch of right MCA (red arrow) are observed.
Raw data TOF MRA
MIP image MRA
MIP image MRA
Bilateral encephaloduroarteriosynangiosis. Collaterals at the site of anastomosis demonstrate prominent flow voids on the raw data image (arrow). Note the hypertrophied parietal branch of STA entering the calvarium (yellow arrow).

24. Perioperative ischemia
Perioperative period can pose risk of ischemia and infarct. Patient developed bilateral frontal infarct following left encephaloduroarteriosynangiosis. MRI permits the accurate assessment of parenchymal changes associated with surgery.

25. MR perfusion in Moya Moya
Several techniques permit assessment of cerebral perfusion including MRI, CT, SPECT and PET . MR perfusion can be assessed with post-contrast dynamic perfusion and arterial spin labelling technique. Diamox challenge can help identify tissue at risk and guide treatment decisions. MR perfusion permits assessment of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) maps.
DSA
MRA
Dynamic contrast enhanced MR perfusion. CBF demonstrates decrease in BF RMCA territory particularly in the frontal lobe (arrow). CBV shows increased BV in right MCA and bilateral ACA, particularly on the right side. MTT shows delayed transit RMCA and bilateral ACA. (arrows)
Note the excellent correlation between DSA and MRA. Severe stenosis is evident in the right carotid terminus with nonvisualization of RA1 from occlusion. Left is also occluded with failure to visualize the ACA branches on bilateral carotid injections. Note the fetal origin of left PCA. The posterior circulation is intact with left P1 hypoplasia from developmental variation.

26. Conclusions Moya Moya disease is an uncommon condition.
The disease can present with ischemic or hemorrhagic stroke, with ischemic strokes more common in the pediatric population.
It is characterized by development of progressive stenosis carotid terminus with development of collaterals.
DSA is considered the gold standard to diagnose. MRI is the noninvasive imaging technique of choice. MRI and MRA can reliably demonstrate several neuroimaging features, satisfying the diagnostic criteria for Moya Moya disease.
MRI and MRA can be used to monitor the progress of the disease and guide treatment. MR perfusion may help identify cerebral parenchyma at risk.
Post surgical changes and associated improvement and complications can be recognized with MRI and MRA.

27. References
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