| Author: | Du, Heng |
| Title: | Validation of CT-identified intracranial arterial calcification as a novel imaging biomarker for reperfusion therapy of ischemic stroke patients : serial hospital-based clinical research |
| Advisors: | Chen, Xiangyan (HTI) |
| Degree: | Ph.D. |
| Year: | 2023 |
| Subject: | Diagnostic imaging Atherosclerosis Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | xix, 145 pages : color illustrations |
| Language: | English |
| Abstract: | Background and purpose Intracranial arterial calcification (IAC) is an independent risk factor for ischemic stroke. For the past years, IAC has been regarded as a proxy of intracranial atherosclerosis based on the high frequency of IAC detection in atheromatous lesions. However, despite the correlations identified between stroke occurrence and IAC, there are still controversies about the connections between IAC and stroke, such as specific cerebrovascular disorder and detailed mechanisms. Serial autopsies showed that there are mainly two patterns of IAC: intimal IAC that involves the intima and medial IAC that is present within the media of the vessel wall. Intimal IAC more frequently coexist with progressive atherosclerosis while medial IAC is associated with arterial stiffness. The difference in pathology may lead to diverse consequences in imaging manifestation, plaque vulnerability and the outcome of treatment. In this thesis, we aimed to delineate the associations between cerebrovascular diseases and different patterns of IAC (intimal and medial) by serial multimodal imaging-based studies. Methods and Materials This hospital-based research consecutively recruited patients with acute ischemic stroke or transient ischemic attack who were scanned by brain computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and high-resolution MRI (HR-MRI). Brain CT was used to examine the presence, patterns and severity of IAC (intimal IAC and medial IAC). MRI was used to evaluate the presence of white matter hyperintensities (WMH) and the infarct pattern in ischemic stroke patients. MRA and HR-MRI were used to assess arteriosclerotic lesions using detailed imaging features including luminal stenosis, eccentric plaque, plaque burden and intraplaque hemorrhage (IPH). The association between IAC pattern and reperfusion treatment was assessed based on the recovery in neurological function in the acute stage of ischemic stroke. For patients who had reperfusion therapy, neurological dysfunction before and after the treatment was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed within 10 days after reperfusion treatment. The etiology of ischemic stroke was assessed based on TOAST classification. Results To investigate the correlations between IAC pattern and intracranial large artery arteriosclerosis, we examined 460 intracranial artery segments from 69 consecutively included stroke patients aged between 18 and 80 years old. Bilateral intracranial internal carotid arteries (ICA), middle cerebral arteries (MCA), intracranial vertebral arteries (VA) and the basilar artery (BA) in each patient were screened using non-contrast brain computed tomography (CT) and high-resolution magnetic resonance imaging (HR-MRI). The results showed that intimal IAC was frequently detected in the cavernous (34.3%) and supraclinoid-to-ophthalmic (30.3%) segments of ICA and the V4 segment of the VA (24.2%), while medial IAC was more prevalently present in the cavernous (43.5%) and supraclinoid-to-ophthalmic (40.3%) segment of the ICA. After comparing atherosclerotic lesions assessed by HR-MRI, the results showed that artery plaques with intimal IAC more frequently coexisted with luminal stenosis (p=0.003), eccentric plaque (p=0.02), higher plaque burden (p=0.001) and IPH (p=0.001), compared with medial IAC and non-calcified artery segments. Medial IAC was not associated with these imaging features of large artery arteriosclerosis. Analysis on the correlations between WMH and IAC pattern showed different results. We assessed WMH with a detailed eight-grade criteria and categorized the severity of WMH into mild WMH, moderate WMH and sever WMH. To further investigate the correlations between IAC and WMH, we also categorized IAC into diffuse IAC and focal IAC based on its involvement in the affected artery segment. In total, 265 patients were included. Intimal IAC was in 54.7% patients and medial IAC in 48.5% patients. Diffuse IAC was in 74 patients, which were all medial pattern. The analysis showed that medial IAC was independently correlated with the presence of WMH (p<0.001). Moreover, after categorizing the severity of WMH, it was found that patients with more severe WMH were more prone to have higher amount of artery segments affected by medial IAC (p<0.001) and higher involvement (diffuse IAC) of medial IAC in individual artery segment (p<0.001). For the correlation between IAC pattern and reperfusion therapy, a total of 130 patients who had either intravenous thrombolysis (IVT) or IVT plus endovascular thrombectomy (EVT) were included. Diffuse IAC was associated with higher baseline NIHSS (p=0.011) and less frequent FNO (p=0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p=0.002) and less FNO (p=0.024). No significant association was found between END and different IAC patterns. As for the correlations between IAC pattern and the etiology of ischemic stroke, we mainly focused on three most common etiologies: large artery atherosclerosis, small vessel occlusion and cardioembolism. A total of 279 acute ischemic stroke patients were included, with 52.0% having small vessel occlusion, 41.2% having large artery atherosclerosis and 6.8% being identified to have cardioembolism. Statistical analysis suggested no significant difference in stroke etiology between patients with intimal IAC and patients with medial IAC. Conclusions The associations with cerebrovascular disease between intimal IAC and medial IAC are different. Intimal IAC is more correlated with large artery arteriosclerosis and is associated with features that may indicate higher risk of ischemic stroke. On the contrary, medial IAC is more correlated with the presence and severity of cerebral small vessel disease. By affecting cerebrovascular beds differently, intimal IAC and medial IAC may have different effects on reperfusion therapy: patient who were more widely involved by medial IAC tended to have more severe neurological dysfunction and less favorable outcome in the acute stage of ischemic stroke. Since the formation of IAC is more of a chronic process of systematic calcification, the impact of IAC pattern on general stroke etiology may be less significant. Future studies on more sophisticated stroke mechanism such as hypoperfusion, artery-to-artery embolism and penetrating artery occlusion may be needed. |
| Rights: | All rights reserved |
| Access: | open access |
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