Differentiation of Deep Subcortical Infarction Using High-Resolution Vessel Wall MR Imaging of Middle Cerebral Artery

Deep subcortical infarction involving the basal ganglia, corona radiata, and/or internal capsule is often categorized into larger subcortical infarction (striatocapsular infarction [SC-I]) and smaller lacunar infarction (lenticulostriate infarction [LS-I]) (1). Being a large artery disease (LAD), occlusion of perforating branches by an atherosclerotic plaque in the middle cerebral artery (MCA) is a prevalent cause of SC-I (2, 3). Conversely, LS-I is also classified as a small-vessel occlusive disease (SVO), related to small-vessel lipohyalinosis (3, 4). The differentiation between SC-I and LS-I is clinically important, since differing pathogenesis of SC-I and LS-I necessitates different clinical managements; systemic anti-atherosclerotic medication, such as statin, may be effective in patients with SC-I, whereas blood pressure management with anti-platelet agents may be useful in patients with LS-I (5). However, LAD may also cause small LS-I due to the protrusion of an atherosclerotic plaque into the orifice of the perforators, occluding the lumen (4, 6, 7, 8, 9, 10). Accordingly, deep subcortical infarctions with different vascular pathologies may have similar shape and location. Therefore, differentiating between SC-I and LS-I as the pathogenesis of LAD and SVO, is challenging (1).

High-resolution vessel wall imaging (HR-VWI) is a useful tool to image intracranial arteries, including MCA (11, 12, 13, 14, 15). It is able to determine the mechanism of stroke, such as atherosclerosis, plaque rupture, and plaque growth over the perforator ostia (16, 17). In 2015, Ryoo et al. (16) applied HR-VWI to differentiate the vascular pathology in deep subcortical infarctions. Deep subcortical infarctions were classified as branch occlusive disease (BOD) (where parent arterial disease occludes the perforator's orifice), and the non-BOD (caused by artery-to-artery embolism). They discovered the characteristic plaque remodeling pattern, location and enhancement in the BOD groups compared to the non-BOD groups (16). However, based on the above classification, the BOD and non-BOD were comprised solely of LAD, and not SVO. Moreover, since BOD and non-BOD were defined by the location of the infarction on magnetic resonance imaging (MRI) (16), the BOD group could have included patients with underlying SVO. Therefore, this study had limitations in the differentiation between LAD and SVO in deep subcortical infarction confined to the striatocapsular region.

To overcome this limitation, our study divided the patients with deep subcortical infarctions into two groups: the SC-I group and the LS-I group. The concept of adopting concept of SC-I and LS-I was to include deep subcortical infarctions developing from both LAD and SVO, and to better assist in the differentiating the underlying stroke mechanism in LAD and SVD. With the use of HR-VWI, we aimed to evaluate the characteristic findings of MCA plaque in patients with deep subcortical infarctions, further distinguishing the difference between SC-I and LS-I. To summarize, our study aimed to evaluate the utility of HRVWI of MCA, and to compare the HR-VWI findings between SC-I and LS-I.

Our results revealed that patients with SC-I had more severe stenosis at MCA than patients with LS-I. According to HR-VWI, the MCA plaque was more frequent and extensive in SC-I than LS-I. More importantly, intraplaque T2-HSI and plaque enhancement were more frequently detected in SC-I than in LS-I. Therefore, HR-VWI provided characteristic MCA plaque findings, and could help to differentiate between SC-I and LS-I.

Many studies have utilized HR-VWI to determine the mechanism of ischemic stroke by revealing the underlying MCA plaque morphology in deep subcortical infarctions (11, 12, 13, 14, 16, 26). Deep subcortical infarctions could develop as LAD from atherosclerosis in MCA, or as SVO from perforator occlusion (1, 2, 3, 4, 7, 9, 27). One previous study classified deep subcortical infarctions from LAD into either BOD by parent artery disease causing perforator orifice occlusion, or non-BOD by artery-to-artery embolism, in accordance with the presence or absence of infarction outside the striatocapsular region, such as cortical infarction (16). As a result, BOD was associated with milder stenosis, more frequent positive remodeling, as well as more frequent and more eccentric plaque enhancement in MCA than non-BOD. However, patients with deep subcortical infarctions from underlying SVO were not included in this study. Nevertheless, since deep infarctions confined at the striatocapsular region can also result from SVO, the definition of BOD can be limited to reflect the underlying pathology of LAD.

To overcome this limitation, we adopted the classification of SC-I and LS-I in deep subcortical infarctions. We believe that the differentiation between LAD and SVO in deep subcortical infarctions without evidence of distal embolism, is also important in patient management. SC-I refers to the infarctions restricted to the basal ganglia and corona radiata which do not extend to the overlying cortex, with typical shape and clinical features (4, 9, 27). SC-I may result from atherosclerotic stenosis of the ipsilateral carotid artery or MCA, or from cardiac or artery-to-artery embolism, rather than small vessel lipohyalinosis (13, 7, 9). Accordingly, the size of SC-I is considered to be greater than 2–3 cm (1, 27), with severe clinical symptoms including hemiparesis, aphasia, neglect, or apraxia (B28). Conversely, LS-I is a typical small deep lacunar infarction resulting from arteriolosclerosis of the small penetrating arteries by lipohyalinosis and angionecrosis (1, 9). Therefore, LS-I can be determined by its small size–usually smaller than 1.5 cm (1, 3)–and its benign clinical course (1). However, small deep subcortical infarctions can sometimes result from LAD or cardioembolism rather than SVO, showing similar size and symptom with LS-I, while at the same time showing a pathogenesis similar to SC-I (1). As a result, SC-I and LS-I can share similar morphological features and clinical manifestations, making it difficult to differentiate the underlying vascular pathology in intermediate-sized deep subcortical infarction (1).

In our study, we employed HR-VWI to compare the characteristic findings of MCA plaques between patients with SC-I and LS-I. Overall, HR-VWI revealed MCA plaque in 72 of 81 patients with SC-I, and in 48 of 64 patients with LS-I. There were more patients who showed atherosclerotic MCA plaque on HR-VWI than those who demonstrated luminal stenosis on TOF-MRA (63 SC-I, 41 LS-I). This mismatch can be explained to some degree, as follows. First, the resolution of TOF-MRA was lower than that of HR-VWI. The voxel size for TOF-MRA was 0.5 × 0.35 × 1.2 mm (0.21 mm³), while that for HR-VWI was 0.5 × 0.2 × 1 mm (0.1 mm³). This probably allowed HR-VWI to delineate finer structures in MCA than in TOF-MRA. Second, previous studies have already reported that HR-VWI could reveal abnormal wall thickening in the patent artery which appear to be normal on TOF-MRA (18, 19, 20). It has been concluded that this phenomenon may be due to arterial adaptation to plaque development, causing positive arterial remodeling (18, 29).

Notably, MCA stenosis on TOF-MRA was more severe, and the plaque on HR-VWI was more frequent, with greater extent in SC-I patients than in LS-I patients. This demonstrates that atherosclerosis of MCA is a more frequent cause of SC-I than of LS-I. Importantly, the parameters for vulnerable plaque, including T2-HSI and plaque enhancement (14, 23, 24, 25), were more frequently detected in SC-I than in LS-I. Therefore, the vulnerable MCA plaque also contribute to the development of infarction with an underlying pathology of LAD. In 2012, Kim et al. (14) determined the infarction pattern using HR-VWI, and they discovered that 1) the vulnerable plaque was frequently associated with artery-to-artery embolic infarction, 2) stable plaque was more associated with in situ thrombosis or SVO, and 3) patients without plaque mostly had SVO. These findings are in line with our results. Here, we show that the plaque is more extensive in patients with SC-I than in patients with LS-I. However, our results suggest that vulnerable MCA plaque is capable of creating SC-I, without the development of cortical artery-to-artery embolic infarctions. Hence, we can assume that the incidence of vulnerable plaque may also be high in SC-I, without any evidence of distal embolic infarction. Indeed, when we compared the number of SC-I and LS-I according to the presence of symptomatic MCA plaque on HR-VWI (13, 14, 23, 24, 25), the incidence of SC-I was higher in patients who had symptomatic plaque findings.

Imaging findings of patients who only had acute infarctions at the time of HR-VWI were analyzed separately. The purpose was to overcome the limitation of the temporal discrepancy between the onset time of infarction and the imaging time. According to the analysis, cases with both acute and chronic infarctions show a similar trend to those with only acute infarctions. It is verified that the imaging time of HR-VWI did not significantly affect the result of our study.

Although the plaque extent and plaque vulnerability assessed by T2-HSI and plaque enhancement (14, 23, 24, 25) were larger in SC-I than in LS-I, we should carefully consider the sizeable proportions of LS-I cases showing similar features to SC-I. Especially regarding plaque vulnerability, 20.3% of acute and chronic LS-I showed intraplaque T2-HSI, and 39.1% of them showed plaque enhancement. In 2012, Chung et al. (20) performed HR-VWI in patients with LS-I, and they reported a surprisingly high prevalence of parent artery branch atheromatous plaques. In accordance with this previous report, our study suggests that small-sized LS-I develop from symptomatic plaque in MCA, which should therefore be categorized as LAD, and not SVO. Likewise, we were unable to detect any MCA plaque in 11.1% of acute and chronic SC-I. In fact, the occlusion of perforating artery causes infarction with a maximal diameter of up to 3 cm (1). This indicates that categorizing SC-I as LAD, and LS-I as SVO, solely based on size criteria can be incorrect and misleading for the clinical management of the patient. Therefore, we recommend that HR-VWI should be used to precisely assist in the subtyping of SC-I and LS-I in deep subcortical infarction.

Regarding the plaque location, a previous study reported that superior wall plaques near the orifice of LSA were more likely to be symptomatic, resulting in larger penetrating artery infarction (13, 26). However, our results showed that the location of the plaque did not significantly differ between SC-I and LS-I. We believe that this was due to the limitation of the assignment of plaque location on the short-axis views. On longitudinal morphological analysis, the plaque can be divided into mid-point and shoulder area, where the plaque shoulder is more prone to rupture (30, 31, 32). Based on this, we assume that if the inferiorly-located plaque is large enough to place its shoulder at the LSA origin, it can cause LSA occlusion and symptomatic infarction by plaque rupture. Indeed, our results showed that plaque extent was significantly larger in SC-I than in LS-I, thereby supporting the above explanation. Hence, we speculate that plaque location could not be used in differentiating between SC-I and LS-I. Rather, under the presence of the MCA plaque, the focus should be on the evaluation of plaque vulnerability on HR-VWI, for good patient management. In addition, LSA itself is still limited to be visualized on 3T MRI, since it has a small diameter ranging from 0.3 to 0.7 mm (33, 34). A future progress in the resolution of HR-VWI or the utility of 7T MRI (33) may enable a proper evaluation of the relationship between MCA plaque location and LSA origin.

Our study has some limitations. First, the atherosclerotic plaques in MCA were not histopathologically confirmed. However, since all patients in our study survived infarction, the pathological confirmation was impossible. Second, as mentioned before, the resolution was not sufficient to provide a clear evaluation of LSA itself. The visualization of LSA and its orifice at MCA would provide substantial information regarding vascular pathology, and concrete evidence for the development of SVO. Therefore, further efforts should be made to improve the resolution of HR-VWI. Third, we evaluated the plaque extent by dividing MCA into 6 divisions, and calculated the number of divisions occupied by the plaque. A measurement of the plaque volume would have been a more accurate approach, but we believe that this was a convenient method to estimate the axial extent of the MCA plaque. Lastly, our scan range was approximately 16 mm, which may not have covered the entire length of the M1 segment of MCA. However, since the main purpose of our study was to evaluate the plaque in the M1 segment that contributes to the development of the deep subcortical infarction, we pre-adjusted the scan range of the M1 segment for each individual patient to include the LSA origin, by confirming the proximal portion of the infarction on DWI and by rough tracing the signal of LSA on the source images for TOF-MRA. After approximating the LSA origin on the M1 segment, more than 50% of the M1 segment was encompassed, with certitude of the inclusion of the LSA origin.

In conclusion, both SC-I and LS-I have similar HR-VWI findings of the MCA plaque, but SC-I had more frequent, larger plaques with greater T2-HSI and plaque enhancement. Therefore, HR-VWI may have a promising role in assisting in the differentiation of underlying mechanism between SC-I and LS-I.