It has been demonstrated that the high prevalence of ICAS in Asians may be at least partially explained by vulnerability to certain risk factors, levels of antioxidant enzyme activity,45,5 and greater intracranial arterial tortuosity than in other races.6 The stroke mechanism also differs according to the location of the atherosclerosis, and most strokes related to extracranial atherosclerosis are caused by artery-to-artery embolism. ICAS is associated with more diverse mechanisms based on the lesion pattern presented on diffusion-weighted imaging: 1) local branch occlusion, 2) artery-to-artery embolism, 3) in situ thrombosis, and 4) hemodynamic. Local branch occlusion is caused by obliteration of the perforator’s orifice by the atheroma. Artery-to-artery embolism manifests as infarcts distal to the stenosis in the territory of the relevant artery, usually with small scattered lesions. In situ thrombosis involves infarcts with extensive involvement of most or even all of the diseased arterial territory. With a hemodynamic impairment, the infarcts are located in the border-zone areas associated with perfusion deficits distal to the stenotic or occluded artery.4,7 ICAS in the anterior circulation, and especially the distal internal carotid artery (ICA), is more commonly associated with artery-to-artery embolism, whereas local branch occlusion is prevalent in posterior-circulation ICAS, especially in the basilar artery (BA).4 In the middle cerebral artery (MCA), the mechanism differs according to the location and severity of the atherosclerotic lesion. In proximal MCA disease, and particularly in the case of proximal MCA occlusion, stroke most commonly results from a combination of mechanisms. This can be explained by plaque rupture with occlusion causing both perforator infarction and embolism. In the case of distal MCA atherosclerotic disease, artery-to-artery embolism is the most common mechanism of stroke because of the location, being associated with turbulence at the distal MCA bifurcation. A longer stenosis is associated with the occurrence of a local branch occlusion.8

High-spatial-resolution in VWMRI is essential for characterizing vessel-wall pathologies, enabling visualization of the morphology of both the plaque and its components. In terms of hardware, a magnetic field strength of at least 3 T is needed to perform VWMRI.9 For vessel-wall assessment, a combination of multiple magnetic resonance sequences such as T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and proton-density (PD) and time of flight (TOF) imaging are used in VWMRI. Multiple tissue-weighted images such as obtained in T1WI, T2WI, and PD imaging are used for better characterization of the individual lesion, whereas TOF imaging is used mainly to characterize luminal abnormalities and locate and assess the site of vessel narrowing. In brain tissue, the signal intensity (SI) on T1WI is highest for lipids, followed in decreasing order by cerebral white matter, cerebral gray matter, and cerebrospinal fluid (CSF). Subacute hemorrhages and high-protein-containing lesions such as mucoceles also have a high SI. On T2WI, the SI in the brain is highest in the CSF, which has the longest T2 relaxation time, followed in decreasing order by gray matter and white matter. Brain edema, demyelinating lesions, cerebral infarcts, and tumors also have long T2 relaxation times and thus a high SI on T2WI. Conversely, acute or chronic hemorrhage, calcification, fibrosis, and high-protein-containing lesions have a low SI on T2WI. PD imaging has a better signal-to-noise ratio than T1WI, while contrast enhancement is less evident.9

Atherosclerosis develops in the inner curvature of the arterial vessel wall, where the shear stress is low.10 Atherosclerotic plaques are composed of lipid, fibrous components, cellular material, connective tissue matrix, and calcification. Evaluating these components can aid the diagnosis of vascular pathologies, thus helping to identify “vulnerable” plaques that are at high risk of causing stroke.11 ICAS lesions are often multiple and exhibit eccentric thickening with or without a focal enhancement (Fig. 1). Positive vessel-wall remodeling can be also observed in some cases.12 Symptomatic plaques are associated with more positive vessel-wall remodeling, intraplaque hemorrhage, and increased vessel-wall enhancement. The aspects of VWMRI findings used to differentiate ICAS from other vascular pathologies and to identify vulnerable plaques are described below.

VWMRI IN NONATHEROSCLEROTIC DISEASEMoyamoya disease (MMD) is an idiopathic, progressive cerebrovascular disease that is characterized by stenosis or occlusion of the distal portion of the ICA and the proximal segments of the MCA and anterior cerebral artery.28 The progressive nature of this disease results in the formation of a fine meshwork of collateral vessels, named Moyamoya vessels. Although these vascular changes generally occur bilaterally, unilateral vascular involvement is often observed in adult-onset MMD.29 Changes in the inner diameter of the vessel are not apparent in the very early stages of MMD.

The gold-standard diagnostic tool for MMD is DSA. However, DSA is relatively invasive and may cause procedure-related complications. Conventional MRA or CTA are noninvasive, but have poor sensitivity in detecting basal collateral vessels.30 VWMRI is a noninvasive technique that has the advantage of allowing the evaluation of vascular-wall pathology. Patients with ICAS often present with positive remodeling of the stenotic lesion, while their counterparts with MMD usually present with smaller outer diameters and negative remodeling qqqon VWMRI (Table 2).31 Histopathological studies have demonstrated that the vessel outer diameter is smaller in patients with MMD than in their non-MMD counterparts.32 Several VWMRI studies have shown that the affected vessels in MMD undergo negative remodeling, resulting in a reduction in the ratio of the outer-vessel-wall boundary area at the lesion site to that at the reference site.31 In the lesion at the site of the stenosis, atherosclerotic plaques usually present with an eccentric pattern and a heterogeneous SI, while in MMD these plaques often exhibit a concentric pattern and a homogeneous SI (Fig. 2).33 The histopathological findings of vessels in MMD, which are reflected on VWMRI, are intimal thickening with increased smooth-muscle cells or endothelium.34 Whether or not the vascular stenosis is enhanced remains to be established, with findings varying between studies. However, when this enhancement is observed in MMD, focal enhancement is not as common as in ICAS,33 and reportedly exhibits a relatively concentric pattern.28 The location of the vascular stenosis is also a diagnostic clue in MMD, with steno-occlusion of the affected vessel usually beginning in the anterior circulation and then proceeding to the posterior circulation.31,33

Intracranial arterial dissection (IAD) is an important cause of stroke, especially for young patients, accounting for up to 20% of cases in this population. Whereas extracranial artery dissection (EAD) predominates (90%) in Western countries, IAD is more frequent (67-90%) in Asian countries,35,36 where the VA is the most common dissection location.35-37 Dissection manifests in various ways, including ischemic symptoms and subarachnoid hemorrhage (SAH). Ischemic stroke and transient ischemic attack present in about 60% of patients with EAD and in 30-78% of those with IAD.36 IAD presents as SAH in 20-60% of patients and accounts for 3-5% of all SAHs.36 Clinical outcomes after dissection are generally favorable, with a particularly low annual recurrent ischemic stroke rate of 0.3-2.4% for EAD, and a low rate of 2-14% for IAD compared with 19% for ICAS.36

VWMRI is useful for diagnosing arterial dissection even if conventional luminal angiography does not reveal the typical features. The characteristic features of arterial dissection are an intimal flap, double lumen, intramural hematoma, aneurysmal dilatation, tapered stenosis, and occlusions (Table 2). Among these findings, the intimal flap and double lumen are pathognomonic features according to the criteria of the Strategies against Stroke Study for Young Adults in Japan.38 However, the detection rate of these signs on DSA is reportedly less than 10%; the detection rate of an intimal flap on VWMRI has been reported to range from 42% to 91%.36 The presence of an intimal flap indicates tearing of the intima and is thus regarded as direct evidence of arterial dissection. This flap appears as a hyperintense curvilinear line that is separated from the vessel lumen on T2WI (Fig. 3). A false lumen is created when blood dissects through the arterial wall and re-enters the vessel lumen. Together with the true lumen, this feature is labeled the double-lumen sign.

The incidence of intramural hematoma, one of the most common findings of IAD, ranges from 61% to as high as 100%.35,39 It may occur as a result of either direct intimal tear with penetration of the blood (subintimal hematoma) or extravasation from the vasa vasorum (subadventitial hematoma). Intramural hematomas are typically described as crescent-shaped thickenings of the arterial wall, which compress the lumen to cause steno-occlusion or dilatation of its external diameter, leading to aneurysmal change. The shape of the hematoma is associated with the presence of ischemic symptoms.40 Intramural hematomas have high SI on T1WI due to an increased methemoglobin component during the subacute stage (2 days to 2 months). However, the SI changes according to the age of the hematoma: during the acute stage (1-2 days) they are hypointense on T1WI and T2WI, becoming isointense after 2 months, rendering their detection difficult.39,41 Susceptibility-weighted imaging is also used for the detection of intramural hematomas. Differentiating between an intramural hematoma and hemorrhagic intraplaque rupture is sometimes difficult. Subintimal hematoma causing stenosis is difficult to distinguish from intraplaque hemorrhage with negative remodeling, and subadventitial hematoma with aneurysmal dilatation is likely to be confused with an intraplaque hemorrhage with positive remodeling. Therefore, clinical information such as cardiovascular risk factors and age, together with other radiological findings is required to distinguish them.35,36

While the pathogenesis of vessel-wall enhancement is not yet fully understood, it is thought to be associated with inflammation, enhancement of the vasa vasorum, slow blood flow through a false lumen, or thrombosis formation from the intramural hematoma.35 The findings of several studies suggest that the enhanced portion of an intramural hematoma represents intramural thrombus formation and that this is associated with increased risk of ischemic stroke.42 The enhancement pattern of a dissection tends to be eccentric and sometimes extends beyond the extent of the intimal flap and/or hematoma, suggesting that the affected area would be larger than just the site of the dissection.

Aneurysmal dilatation is caused by the accumulation of blood through the dissection site, which subsequently cleaves vessel layers, especially between the media and adventitia. A VWMRI study found that aneurysmal dilatation was the most common finding of IAD, accounting for 67% of all cases.43 Rupture of an intracranial dissecting aneurysm leads to SAH. The intradural segment of the VA is the site of SAHs in more than 50% of cases.43 Although not specific signs, the presence of a fusiform or irregularly shaped aneurysm and location in a nonbranching arterial site with segmental stenosis can raise suspicion of dissection.

In the chronic stage, an intimal flap, double-lumen sign, aneurysmal dilatation, and intramural hematoma tend to disappear. However, some cases demonstrate persistent mild enhancement with focal vessel-wall thickening in the chronic stage, even if the stenosis has completely resolved. It is our opinion that these changes may be attributable to compensatory intimal hyperplasia. Stenosis resolution was shown to occur in up to 90% of EAD patients,44 while the rate of improvement of stenosis among IAD patients varied markedly between studies, from 20% to 84%.35,36 Improvement in stenosis usually occurs within 3-6 months of the dissection event and is rarely observed after 6 months.41,44

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical and radiological syndrome that manifests with the primary clinical features of sudden onset of severe headache and diffuse segmental vasoconstriction of the cerebral arteries that resolves within 3 months.45 However, RCVS is not a single disease entity, and its diagnosis can be challenging due to its symptoms and signs overlapping with those of a range of other central nervous system (CNS) diseases that are accompanied by the sudden onset of severe headache. Multifocal segmental cerebral artery vasoconstriction demonstrated on either DSA or indirectly on CTA/MRA that normalizes within 12 weeks after onset is a characteristic finding of RCVS.

VWMRI can differentiate the distinct characteristics of arterial-wall thickening and arterial-wall enhancement, which can be helpful for the timely and accurate diagnosis and management of RCVS and the overlapping non-RCVS disease entity.46,47 Recent studies have identified characteristics of arterial-wall thickening and arterial-wall enhancement in RCVS that are distinct from those of CNS vasculitis and SAH.48 Both vasculitis and RCVS exhibit arterial-wall thickening, but RCVS has no or mild arterial-wall enhancement compared with vasculitis (Table 2). When aneurysmal-wall enhancement is observed in vasospasm associated with aneurysmal SAH, it is helpful to rule out RCVS because it indicates inflammation and possible recent rupture. Distinguishing between RCVS and other non-RCVS emergencies is critical due to the significant differences in their treatments and clinical outcomes. The course of RCVS is rather benign, with spontaneous resolution occurring and few complications compared with the other, non-RCVS emergencies; for example, CNS vasculitis requiring immunotherapy and SAH requiring intensive care management and surgical/interventional treatment, usually with a poor outcome. Furthermore, serial monitoring based on noninvasive VWMRI can be useful to differentiate the following dynamic pattern: delay in the appearance of RCVS vasoconstriction that may mimic the typical time course of arterial vasospasm, while hyperacute vasospasm may occasionally be associated with aneurysmal SAH.

CNS vasculitis is a rare disease that can be classified into primary CNS angiitis and secondary CNS vasculitis due to systemic inflammation or infectious conditions.49 Pathologically, vasculitis is characterized by luminal narrowing, wall disruption, ischemia, and hemorrhage due to inflammation of the vessel wall. These characteristics mean that VWMRI, which can visualize vessel-wall inflammation, may be helpful for diagnosing vasculitis. Although visualizing the walls of small intracranial vessels is difficult with the current spatial resolution of VWMRI, this method is useful when the CNS vasculitis involves larger intracranial arteries. CNS vasculitis is typically characterized on VWMRI by smooth, homogeneous, concentric vessel-wall thickening and contrast enhancement, more predominantly in small to medium-sized arteries (Table 2, Fig. 4). This differs from atherosclerotic plaques, in which eccentric and irregular vessel-wall abnormalities occur predominantly in the more proximal intracranial arteries. However, since atherosclerotic plaques sometimes show concentric vessel-wall thickening, vasculitis can also show eccentric vessel-wall thickening and enhancement.

The likely mechanisms underlying arterial-wall enhancement in CNS vasculitis are increased permeability of the endothelium with contrast leakage from the lumen into the arterial wall, and vasa-vasorum-related contrast leakage. Arterial involvement is more common where there are single lesions in multiple different arteries than where there are multiple lesions in a single artery.50 Thus, vasculitis should be suspected when multiple ischemic strokes occur with various ages at onset in different vascular territories.49 The presence or severity of vessel-wall enhancement is not helpful in the differential diagnosis of vasculitis etiology, whereas the distribution of a vascular involvement pattern is. For example, temporal arteritis can be suspected if vasculitis affects the superficial temporal artery and there is concurrent involvement of the intradural ICA or VA. Primary CNS angiitis may be suspected in cases involving medium-sized vessels, such as those distal to the MCA bifurcation, or the anterior or posterior communicating arteries.50 In intracranial artery vasculitis, clinical disease activity and VWMRI findings are not always correlated. However, certain treatments affect VWMRI findings, such as the diagnostic sensitivity of VWMRI decreasing when corticosteroid is administered in patients with temporal arteritis. The different imaging characteristics in intracranial artery diseases on VWMRI are presented in Table 2.

VWMRI is clinically useful, but appropriate imaging techniques and proper interpretation are important for an accurate diagnosis. It is also important to be aware of the potential pitfalls and limitations for the proper application of VWMRI in clinical settings. The clinical implications of an ICAS plaque are understood based on the results of carotid plaque studies, but it is unclear whether the extents of the carotid and intracranial plaques are actually similar. Few studies have correlated histopathological and VWMRI findings. Moreover, it is difficult to achieve adequate spatial resolution with VWMRI of ICAS, and caution is needed when interpreting the findings relative to those obtained for carotid plaques. Therefore, certain factors should be considered in the interpretation. First, slow vascular flow can cause the loss of flow voids and mimic vessel-wall enhancement.9,51 The VWMRI technique relies on blood flow for blood-signal suppression. Since the blood in a vessel exhibits laminar flow, the velocity is lower closer to the vessel wall. Therefore, the area adjacent to the vessel wall may exhibit incomplete signal suppression, giving the impression of vessel-wall thickening or enhancement. Artifacts are also likely to occur as a result of recirculating or slow blood flow due to an aneurysm or dilated artery, and retrograde filling through a leptomeningeal collateral due to proximal arterial occlusion.

Second, the blood supply to the vasa vasorum of the intracranial arteries may appear like concentric arterial-wall thickening and concentric enhancement, potentially mimicking vasculitis.9,51 The vessel wall of the extracranial arteries receives its blood supply through the vasa vasorum, whereas the intracranial arteries rely less on the vasa vasorum, which Second, the blood supply to the vasa vasorum of the intracranial arteries may appear like concentric arterial-wall thickening and concentric enhancement, potentially mimicking vasculitis.9,51 The vessel wall of the extracranial arteries receives its blood supply through the vasa vasorum, whereas the intracranial arteries rely less on the vasa vasorum, whichais smaller than in extracranial arteries, due to the influence of the adjacent CSF. Aging and atherosclerotic risk factors cause the extracranial vasa vasorum to extend to the proximal intracranial segment of the ICA or VA, and the vasa vasorum develops in the intracranial arteries. In the presence of ICAS, the vasa vasorum can develop more distant from the extracranial vasa vasorum,17 causing concentric arterial-wall thickening and enhancement, mimicking vasculitis.

Third, in the case of mechanical thrombectomy, concentric intracranial arterial-wall thickening and enhancement may be seen due to mechanical injury of the arterial wall. Thus, post-thrombectomy enhancement can be misdiagnosed as CNS vasculitis.52 Finally, venous enhancement adjacent to arteries can also mimic vessel-wall enhancement.9,51 This problem can be avoided by performing VWMRI with multiple planes and comparing the images with MRA findings.