If a symptomatic patient remains undiagnosed and untreated, it results in irreversible neurological deficit, especially in pediatric patients [6– 8] . Therefore, MRI/MRA must be performed without hesitation in pediatric patients with ischemic stroke or transient ischemic attack (TIA).
Evaluation of Treatment Strategies
Once a patient has been diagnosed with moyamoya disease, the patient should undergo further MR analysis to assess the present condition. First, it is important to evaluate the degree of disease progression, regardless of whether or not surgery is planned. An MRA can be employed to determine the disease stage, which was previously decided by conventional angiography [9] . Second, an evaluation of parenchymal damage by MRI is also essential to predict the outcome and to determine appropriate surgical strategies. Third, a hemodynamic study is required before surgery. Although existing modalities are reliable, recent MRI techniques can be utilized to roughly assess the cerebral hemodynamics without exposure to ionizing radiation [10– 14] . Finally, several findings seen on MRI/MRA indicate an increased risk for future stroke including infarction and hemorrhage. Accordingly, such findings should be taken into consideration when determining treatment strategies.
Follow-Up
After surgery, it is essential to evaluate the development of a collateral pathway via the external carotid artery (ECA) system and subsequent changes occurring in intracranial arteries.
Although MRA is inferior in spatial resolution to angiography, it is capable of demonstrating the serial morphological changes that responded to surgery in a noninvasive way.
Steno-occlusive lesions in intracranial arteries frequently progress naturally in pediatric patients [15– 17] . In addition, a recent report showed that the incidence of disease progression in adult patients is much higher than previously recognized [18– 20] . Hence, careful MRA follow-up is essential in nonoperated cases.
Morphological Evaluation MRI
Although MRI in asymptomatic cases as well as in cases with TIA frequently discloses no abnormality, old ischemic or hemorrhagic lesions are occasionally detected in the brain paren- chyma. These ischemic lesions are commonly seen in anterior or posterior watershed zones [21] , showing bilateral hemispheric distribution. To detect such lesions, T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging is useful. As the disease progresses, steno-occlusive changes in the ICA and its tributaries can be detected as a decrease in the diameter of flow void in T2-weighted images, whereas the posterior cerebral artery (PCA) shows a marked increase in diameter (Fig. 1a ). Around this stage, moyamoya vessels can be
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seen in basal cistern or basal ganglia, and the abnormal fine vessels are clearly depicted as numerous flow voids in T2-weighted images (Fig. 1b, c ).
Leptomeningeal enhancement (ivy sign) on contrast-enhanced T1-weighted images is a characteristic MRI finding of moyamoya disease (Fig. 2 , upper row) [22, 23] , and FLAIR images can also reveal the ivy sign without the use of contrast media (Fig. 2 , lower row) [23, 24] . The ivy sign is due to an engorged pial network via a leptomeningeal anastomosis, which diminishes after bypass surgery with the development of new transdural collateral vessels [22– 24] . However, subarachnoid hemorrhage (SAH), meningitis, and spontaneous intracra- nial hypotension [25, 26] should be considered when the ivy sign is identified.
Recent reports showing T2*-weighted images reveal that asymptomatic microbleeds occur in 15–56% of moyamoya disease patients [27– 29] . Although the clinical implications of the microbleeds have yet to be understood, the presence of multiple microbleeds might be a predictor of subsequent hemorrhagic stroke.
Recent development of high field MRI has made it possible to reveal brain vessel microstructure in moyamoya disease. Coworkers at our institution observed transverse lines (medullary streaks) in white matter using 3-Tesla MRI T2-reversed imaging (Fig. 3 ) and concluded that the increase in medullary streak diameters observed in patients with moyamoya disease represent vessels dilated due to cerebral hypoperfusion [30] .
Once ischemic stroke occurs, diffusion-weighted (DW) imaging is useful to localize ischemic lesions, which are depicted as high intensity areas in the early acute phase (Fig. 4 ).
The main cause of intracranial hemorrhage is rupture of dilated, fragile moyamoya vessels, resulting in intraventricular hemorrhage or intracerebral hematoma (ICH) [31– 34] . Although CT is usually superior to MRI for detecting acute ICH, the ICH commonly shows high intensity on T2-weighted images in the early acute phase, and high intensity accompanied by a low intensity rim on DW images. Rupture of a saccular aneurysm around the circle of Willis causes SAH [34, 35] . For detecting SAH in the acute phase, FLAIR imaging is sensitive [36, 37] . In addition, T2*-weighted images are also helpful in detecting SAH in the subacute and chronic phases, which are generally unclear on CT [37] .
Longstanding brain ischemia results in brain atrophy, which is usually seen in the frontal lobe in the early stage but becomes diffused with progression of the disease [21] .
Fig. 1 Typical findings of moyamoya disease with T2-weighted magnetic resonance imaging (MRI) includes the disappearance of the flow void signal of the terminal portion of the internal carotid artery (ICA; arrow ), the reciprocal dilatation of the posterior cerebral artery (PCA; arrowhead ) ( a ), and the development of many tiny flow voids (moyamoya vessels) in the basal cistern ( arrow ) ( b ) and basal ganglia ( arrow ) ( c )
Fig. 2 Ivy sign. Contrast-enhanced T1-weighted MRI shows diffuse leptomeningeal enhancement ( upper row ). Ivy sign can be identified with fluid-attenuated inversion recovery (FLAIR) images ( arrowheads ; lower row )
Fig. 3 T2-reversed 3-Tesla MRI in a moyamoya disease patients (( a ) axial, ( b ) coronal view) shows transverse lines (medullary streaks) that likely represent vessels dilated due to cerebral hypoperfusion
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MRA
MRA is the most useful modality to diagnose early-stage moyamoya disease, irrespective of the type of acquisition techniques including 3D time-of-flight MRA, phase contrast MRA, and contrast-enhanced MRA [38, 39] . In the very early stage, MRA shows slight stenosis of the ICA terminal portion (Fig. 5a ). As the disease progresses, MRA discloses the typical find- ings of moyamoya disease including the steno-occlusive change in the ICA and its tributar- ies, the development of moyamoya vessels, and an increase in the diameter of the ECA system (Fig. 5b ) [21, 40] . Although Suzuki and Takaku once classified this disease into six stages based on angiographic findings [41] , a novel grading of MRA findings correlates well with angiographic staging [9] . Interestingly, the disease stage does not always correlate with the severity of clinical symptoms, i.e., it is not rare that a patient in an advanced stage remains asymptomatic (Fig. 5b ). In cases of advanced stage moyamoya disease, the PCA frequently shows a marked increase in diameter in a reciprocal fashion. However, it is not uncommon for the PCA to have steno-occlusive changes (Fig. 6 ). Some reports suggested that PCA stenosis correlates with the occurrence of cerebral infarction [42– 44] . Moyamoya vessels originate not only from the ICA but also from the PCA. Some authors have reported that the MRA in hemorrhagic cases shows marked dilatation of choroidal arteries or posterior pericallosal arteries, compared to that in patients experiencing an ischemic event [45, 46] . In addition, the dilatation of thalamoperforating arteries is commonly seen, especially in cases with ICH (Fig. 7 ). Accordingly, these findings on MRA might be a predictor of hemorrhagic events.
Another cause of hemorrhage is saccular aneurysms on the circle of Willis, which occur quite often at the basilar artery [3, 34] and can be easily detected by MRA.
MRA is also the most appropriate modality for postoperative follow-up because of its noninvasiveness. After surgery, MRA can demonstrate not only the development of ECA, including the superior temporal artery (STA), deep temporal artery, and middle meningeal artery, but also the regression of moyamoya vessels or progression of stenotic changes in the ICA [47– 49] (Fig. 8 ).
Fig. 4 Diffusion-weighted (DW) MRI obtained 4 h after ischemic stroke in a moyamoya disease patient reveals the ischemic lesions as a high intensity area in early acute phase
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The development of MR technology has become available for MRA on 3-Tesla MR systems [50, 51] . 3-Tesla MRA depicts moyamoya vessels more clearly than 1.5-Tesla MRA.
In addition, distal branches of intracranial arteries can be clearly visualized by using 3-Tesla MRA (Fig. 6b, c ). However, even though the high field MRA was employed, it seems difficult to identify collateral circulation in peripheral regions including a leptomeningeal Fig. 5 MR angiography (MRA) of two cases with asymptomatic moyamoya disease. ( a ) MRA of a 20-year-old woman with a family history of moyamoya disease shows slight stenotic change of the terminal portion of bilateral ICA ( arrow ). ( b ) MRA of 52-year-old-woman who never had neurological symptoms ever reveals moyamoya disease in a more advanced stage
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anastomosis on the cortical surface or a transdural anastomosis via a vault or ethmoidal moyamoya.
Furthermore, it is also difficult to ascertain the detailed course of STA which is important information for harvesting STA for direct bypass.