Advances in the application of optical coherence tomography in the assessment of ischemic stroke

XU Ding-ji, ZHAO Zhen-qiang, CAI yi

1.Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou 570102,China

Keywords:

ABSTRACT Ischemic stroke has high morbidity, mortality, disability rate and recurrence. It is the one of the main diseases that threaten people's health in China. Its etiology, pathogenesis, and reaction mechanism has been the research hotspot and difficulty of related studies have shown that the optical coherence tomography technology is an effective measure to evaluate ischemic cerebral apoplexy.Optical coherence tomography (OCT) is a gradually developed and mature imaging technology in recent years, and there are related studies on internal carotid artery, retina and coronary artery.Based on the above background, this paper reviews the research progress of optical coherence tomography in the assessment of the etiology, pathogenesis and response mechanism of ischemic stroke.

1. Introduction

Cerebral stroke, also known as cerebral stroke, has two distinct main types, including bleeding and ischemia.Hemorrhage is defined as the accumulation of blood in the cerebral parenchyma and compression of adjacent cerebral parenchyma.Ischemia is defined as insufficient blood flow to meet the brain tissues' demand for oxygen and nutrients.Ischemic stroke is caused by the interruption of blood flow to the brain due to a blood clot, resulting in reduced mobility, cognitive decline and sensory impairment [1].Stroke not only has a high morbidity, mortality, disability and recurrence rate,but also accounts formore than 80% of ischemic stroke. Therefore,15 million patients worldwide are affected by stroke every year[2,3].Optical coherence tomography (OCT) is a highly localized,non-invasive technique that provides absolute and quantitative hemodynamic indicators and cellular status markers to monitor ischemic brain injury and recovery [4].At present, OCT has been gradually developed in clinical practice. In terms of application of carotid artery, it can be used to evaluate carotid artery plaque morphology and stent placement in more detail [5,6,7].a can be detected, which is conducive to the detection of diabetic fundus microcirculation and other fields of research [9,10,11,12].As for ischemic stroke, OCT has been studied on the etiology, pathogenesis and reaction mechanism of ischemic stroke, providing scientific basis for diagnosis, treatment and prognosis judgment.Therefore,this paper mainly reviews the application of OCT in the assessment of ischemic stroke.

2. Traditional imaging of ischemic stroke

Traditional imaging examinations for intracranial vascular diseases include digital subtraction angiography (DSA) and computed tomography (CTA)Angiography), magnetic resonance angiography (MRA) (magnetic resonance angiography), and Doppler ultrasound (DUS) (Duplex ultrasound).DSA is the gold standard for the diagnosis of intracranial vascular diseases, with high sensitivity, specificity and accuracy, but it has the disadvantage of X-ray irradiation.CTA provides three-dimensional visualization by optimizing X-ray exposure, but is inefficient at evaluating blood flow velocity.MRA is another method with high precision and resolution, which is helpful for the characterization of vulnerable plaques, but the equipment is expensive and not readily available anywhere.DUS is low cost, but its efficiency depends on operator skill and experience.Therefore, for patients undergoing DSA and CTA, the disadvantage is that radiation exposure and the risks associated with contrast agent use (e.g., anaphylaxis, contrast nephropathy) may lead to adverse reactions.For patients undergoing MRA examination, the contraindication is that the patient has the relevant metal stent installed in the body, and patients with claustrophobia and adverse reactions related to contrast agents cannot be examined.With regard to the examination of DUS,shortcomings require trained personnel to perform and interpret the presence of intracranial and extracranial vascular disease [13].

3. Features and advantages of OCT

In 1991, Huang et al. developed a technique called optical coherence tomography (OCT), which he first demonstrated in vitro and its application to human retinas and coronary arteries.On the retina, OCT displays images of the retina and optic disc of the human eye.Morphological features of OCT images were directly correlated with histological results.OCT scanning was performed after the cornea and lens were removed to simplify beam positioning.In the human eye, the same measurement can be made using a beam positioning system, similar to those used for scanning laser ophthalmoscopes.OCT imaging of the retina and optic disc has a higher depth resolution than clinical ultrasound or confocal scanning systems.It provides information on the contour and thickness of important retinal structures, which can be used as the basis for new clinical diagnosis.In coronary arteries, the wall of the coronary artery is a clinically important tissue that can be examined by OCT.Laser angioplasty and other techniques used to clear blocked blood vessels in the heart and other organs have been limited by poor resolution of physiological and pathological tissue.However, OCT provides a method for probing the vascular wall in open surgery and catheterbased vascular surgery [14]. The cross-sectional image generated using OCT utilizes backscattered light from the structure of the vessel wall. The basic idea is that the various biological tissues in the body have different optical indices, so different tissue layers inside the blood vessel wall reflect light at different amplitudes.An optical beam splitter divides the light from the laser into reference light and sample light.The backward-reflecting light of the sample light and the reference light is combined in a way that can be either constructive or destructive.It has the function of a vessel wall spatial resolution of 10-15 mm and a vessel wall penetration depth of about 3mm [15]. Compared with traditional angiography, OCT has the following main advantages: (1) it can provide high-resolution images of vascular wall, intracavinal thrombosis, and aneurysm wall, and has good correlation with histological sections; (2) The ability to assess stent dislocation, intimal leakage, and puncture the location of the artery; (3) Accurate evaluation of vascular diameter, selection and placement of ideal stents [16]. The US Food and Drug Administration(FDA) approved the use of intravascular OCT for the diagnosis and treatment of cardiovascular disease in 2010. Interventional neuroradiology specializes in the diagnosis and treatment of vascular diseases of the central nervous system, mainly including carotid atherosclerotic disease and acute ischemic stroke secondary to great vessel occlusion.The appeal of treating vascular diseases through minimally invasive techniques without the need for open surgery has led to continuous technological innovation and device development.The application of intravascular OCT imaging in neurointerventional radiology seems to be natural [15].

4. Application of OCT in the diagnosis and treatment of ischemic stroke

OCT imaging technology is a new imaging technology emerging in recent years, which has opened a new chapter for the diagnosis and treatment of ischemic stroke. For ischemic stroke, OCT imaging technology mainly focuses on the detailed and comprehensive study and evaluation of the etiology, pathogenesis and response mechanism after stroke.

4.1 Post-stroke etiology

After the occurrence of ischemic stroke, how to quickly and accurately find the cause of the disease is very important. OCT imaging technology can be used for etiology monitoring after ischemic stroke. Relevant studies have been reported on two kinds of intracranial vascular diseases, vertebrobasilar artery stenosis and vertebrobasilar artery dissection, which are analyzed one by one in the following.

4.1.1 Evaluation of vertebral basilar artery stenosis

In terms of ischemic stroke, about 1/3 of ischemic cerebral infarction occurs in the vertebral basilar artery system, and vertebral basilar artery stenosis or occlusion is an important cause of posterior circulation stroke [17]. Patients with symptomatic intracranial vertebrobasilar stenosis (diameter reduction50%) had a higher risk of early stroke recurrence, up to 33% within 90 days after the first stroke or TIA.For conventional imaging techniques, OCT has a high resolution (10-20 μm) and has proven useful in the coronary system, and is more commonly used in extracranial carotid arteries to identify vulnerable plaques, assess stent-vessel interactions, and identify marginal dissections.

Relevant studies have shown that OCT angiography can clearly describe the morphological characteristics of intracranial vertebral basilar artery stenosis, including fibrous plaques, luminal thrombosis,mixed plaques, vascular dissection, thin fibrous bonnet, macrophage aggregation, lipid-rich plaque rupture, various calcifications, plaque erosion, etc.By using OCT angiography to identify these features,it can guide the medical treatment of intracranial vertebral basilar stenosis and the intraoperative treatment of angioplasty and stenting[18].Although OCT angiography can detect the microscopic structure and pathological features of the vessel wall, its application in intracranial arteries is still limited.These limitations are in the following aspects. First, the curvature of the intracranial artery may limit the progress of the imaging catheter.Repeated attempts to cross the curvature of the intracranial artery may result in catheter rupture and vascular injury.Second, image quality may be affected due to vascular curvature, with associated artifacts including uneven rotational deformation and undesirable vascular irrigation. Finally, loss of the embolus after the vascular lesion has been cleared may result in a distal embolism.To solve the above problems, the wide application of OCT in intracranial vascular system, by optimizing the OCT imaging catheters (appearance is smaller, more soft hardness) and can and through micro catheterization, and security, flexibly by intracranial artery circuity,view the blood vessel walls can be obtained more complete imaging,especially in cerebral aneurysms. Therefore, using OCT technique to observe stenosis can provide more research tools and data for future research and provide a new research perspective for intracranial vertebral basilar artery treatment [19].

4.1.2 Evaluation of vertebral basilar artery dissection

Vertebrobasilar artery dissection (VAD) refers to a disease in which the vertebral artery or basilar artery intima tear is caused by various causes, and blood enters the vessel wall through the damaged intima to form hematoma, or spontaneous hematoma in the artery wall,resulting in vascular stenosis, occlusion or rupture. It can cause cerebral hypoperfusion, thrombosis and pseudoaneurysm formation,resulting in cerebral ischemia, brainstem compression symptoms and subarachnoid hemorrhage (SAH), etc. [20]. Studies have shown that in patients with intracranial artery dissection (IAD), it is often difficult to make a definitive diagnosis and multimodal imaging is often required to confirm the diagnosis.Based on traditional angiography, computed tomography, or magnetic resonance imaging, OCT can be used to better display the characteristics of IAD. The pathological changes of restenosis can be observed, and the diagnosis of restenosis can be determined to show basilar artery(BA) dissection with residual transverse flap, double lumen, and mural hematoma.Imaging studies at multiple levels revealed intimal rupture originating from the right vertebral artery and extending distally to BA.The use of OCT intravascular imaging makes the diagnosis of IAD more accurate, but should be handled with caution because of the potential for increased field risk to the patient.Therefore, the security of OCT in IAD needs to be further improved[21].

Based on the cause of ischemic stroke after OCT imaging examination of the related studies have shown that OCT imaging in ischemic stroke patients with basilar artery stenosis and the interlayer, as soon as possible the use of the technology to assess,diagnosis, treatment, prognosis and so on, cause can make patients get early treatment, rapid recovery, To prevent the occurrence of related complications and endanger the life of patients.Therefore,OCT imaging technology in the etiological examination of ischemic stroke after continuous development, improvement and clinical application.

4.2 Pathogenesis after stroke

OCT imaging technology plays an increasingly important role in monitoring the pathogenesis of ischemic stroke.Relevant studies have reported that not only the changes of endothelial cells after thrombotomy can be monitored, but also the role of thrombosis,cerebrovascular blood flow and perfusion can be observed.

4.2.1 Evaluation of thrombosis after basilar artery thrombectomy

With regard to the observation of the intravascular structure after endovascular thrombectomy of the basilar artery, relevant studies have shown that MR imaging and animal hiSTOLOGY can detect endothelial injury after endovascular thrombectomy(EVT). However, traditional imaging techniques are limited because MR imaging does not have sufficient spatial resolution to directly display endothelial cells, and histopathological examinations are performed in vitro to provide a real-time pattern of injury. Relevant studies have concluded that OCT imaging after EVT can detect evidence of endothelial injury in real time, and is safe and reliable.It can generate cross-sectional images to show endothelial injury and atherosclerosis in patients with endovascular thrombectomy.In addition, we observed that there may be significant residual thrombosis after EVT, which may lead to progressive stroke and occlusion of the important basilar artery (BA) perforator branch[22].Studies have shown that OCT imaging can accurately quantify vascular wall damage in real time after EVT, which is conducive to the assessment of the occurrence of ischemic stroke [23]. Therefore,the application of OCT imaging in endovascular thrombectomy can prevent progressive stroke.

For ischemic stroke caused by thrombus, animal experimental studies have shown that OCT imaging technology provides a unique way to improve the understanding and evaluation of stroke and treatment for photothrombus (PT) stroke. In order to systematically study the complex mechanism of ischemia and tissue injury, OCT imaging technology will contribute to the clinical treatment of ischemic stroke and other diseases [24].

4.2.2 Cerebrovascular blood flow and perfusion monitoring and evaluation

Ichaemic stroke is a serious acute nervous system disease, which can cause irreversible damage to brain tissue and have a great impact on the quality of life of patients.An ischemic stroke occurs when blood flow to the brain is interrupted or reduced, depriving brain tissue of oxygen and allowing brain cells to begin to die within minutes. Therefore, real-time monitoring of cerebral blood perfusion level is helpful to understand the pathogenesis of the disease. OCT is a non-invasive method that can distinguish between moving particles and stationary tissues to display the level of cerebral perfusion without the use of contrast agents, extending the application of OCT from purely structural imaging to functional imaging.Middle cerebral artery occlusion (MCAO) often results in extensive cerebral cortex ischemia, and the damage varies greatly from individual to individual.In clinical or basic research, comparing the left and right hemispheres is often the most intuitive way to determine the degree of ischemia.Related studies have shown that the scanning source optical coherence tomography (SS-OCT) system has been used to monitor the whole brain microcirculation in MCAO rats for a long time. During ischemia, cerebral perfusion levels in the left and right hemispheres and the whole brain were quantized and compared, while changes in vascular morphology and location were recorded.In conclusion, SS-OCT technique has a whole-brain field of view and capillary resolution, and is a reliable tool for studying cerebrovascular diseases and evaluating potential therapeutic strategies [25].

As for the monitoring of cerebrovascular perfusion by OCT imaging technology, studies have reported that the state of cerebral perfusion reflects the degree of cerebrovascular occlusion and is closely related to the process of post-ischemia injury.Cerebrovascular perfusion density (CVPD) refers to the ratio of "the number of blood vessels with blood flow" to "the total number of blood vessels",and is an indicator of cerebral blood flow perfusion status.Although many imaging techniques have contributed to the quantification of CVPD in animal brains, they have limitations.Magnetic resonance imaging (MRI), positron emission tomography (positron emission tomography), and ultrasound provide noninvasive and functionally relevant imaging of animal angiography, but their limited resolution limits their ability to image the microcirculation.However, OCT angiography is a reliable tool to observe cerebral blood flow,which can comprehensively evaluate the state of cerebral perfusion qualitatively and quantitatively. It is proposed that the quantization of CVPD is effective and can solve the problem of uneven signal distribution in the segmentation of OCT vascular images.The results of MCAO showed that CVPD could be used as an effective indicator to evaluate the injury after cerebral ischemia.OCT angiography in the monitoring of CVPD provides new insights for the study of the mechanism of stroke [26].

In animal studies, laser speckle imaging (LSI) and visible optical coherence tomography (VIS-OCT) have been used to measure changes in cerebral blood flow, vascular morphology, and oxygen saturation before and after distal middle cerebral artery occlusion(DMCAO). Visible optical coherence tomography is based on OCT angiography (OCTA) and spectral OCT to show oxygen saturation measurements at angiographic capillary levels. By combining LSI with VIS-OCT, we were able to show dynamic changes in the acute stage of stroke models in DMCO [27].

Some animal studies have shown that the spatiotemporal dynamic imaging of brain damage caused by blood vessels and cells after acute ischemic stroke based on endogenous light scattering signals provided by OCT imaging can measure the changes of blood perfusion, blood flow, red cell velocity and cortical light attenuation during focal cerebral ischemia in a mouse model. Therefore, multiparameter OCT imaging is helpful for the comprehensive evaluation of ischemic lesions in the early stage of stroke, and will be helpful for the in-depth exploration of the mechanism of ischemic brain injury in preclinical studies and the development of treatment strategies to improve the prognosis of ischemic stroke [28].

The above related studies have shown that OCT imaging technology can timely monitor the pathogenesis of ischemic stroke, and take relevant clinical treatment and prevention to prevent the occurrence of secondary ischemic stroke with the pathogenesis, so as to avoid aggravation of the symptoms of patients again, and even endanger the lives of patients.Therefore, OCT imaging technology is an essential auxiliary examination item for monitoring the pathogenesis after ischemic stroke, and it is hoped that it can be applied in clinical practice for patients with ischemic stroke.

4.3 Mechanism of response after stroke

After ischemic stroke infarcts occur around the core of ischemia and half dark, mainly for tissue repair and micrangium regeneration and functional recovery, brain edema, the emergence of the sidebranch water cycle and related reaction mechanisms, however OCT imaging technology for ischemic stroke after the related reaction mechanism can be high resolution and accuracy of observation.

4.3.1 Brain tissue repair and microvascular regeneration and function evaluation

For the tissue repair and microangiogenesis and function of ischemic stroke, there are related studies that use OCT imaging technology to study the tissue repair and microangiogenesis and function of brain parenchyma after stroke. OCT angiography provides a good contrast to distinguish between ischemic lesions and unaffected brain tissue. Tissue in the deeper cerebral cortex is more prone to cerebral ischemia than in the superficial cortex. Brain tissue repair is accompanied by microvascular regeneration in the ischemic penumbra.In addition, the new capillary network is highly directional, which can optimize blood perfusion in the ischemic area and guide the development of new neurons toward the pathological direction.The degree of microangiogenesis and the size of ischemic lesions are dependent on the depth of the infarction. Deep capillary networks are more directional than shallow ones. The conclusion of this study shows that OCT angiography shows a high degree of directivity in the regenerated capillary networks. This technique is beneficial to observe the recovery of brain tissue and blood vessel damage in patients with clinical ischemic stroke, and is helpful to guide a new strategy for the treatment of stroke [29]. For ischemic stroke due to cerebral vascular obstruction, ischemia leads to cell death and brain tissue damage in the core and induces a series of endogenous vascular and cellular changes in the penumbra.With respect to post-stroke reactions, relevant studies have shown that OCT imaging is a non-labeled, non-invasive, three-dimensional,real-time method for monitoring vascular and cellular responses by utilizing the light scattering properties inherent in red blood cells and brain tissue to produce images with endogenous contrast.OCT angiography (OCTA) and optical attenuation coefficient (OAC)imaging allow the evaluation of experimental ischemic stroke using multiple parameters including capillary perfusion, cerebral blood flow, and cell scattering.Studies have found that the light attenuation coefficient is related to brain tissue degeneration after ischemic stroke, and the increase of OAC may be related to the increase of astrocytes and neuronal death. The results show that the increase of OAC is positively correlated with the change of astrocytes in stroke,and negatively correlated with neuronal response [30].

4.3.2 Evaluation of cerebral edema

As a complication of cerebral edema in ischemic stroke, related studies have shown that the obstruction of the middle cerebral artery can lead to severe cerebral edema, leading to changes in the optical properties of the swollen brain cells, so that changes in brain edema can be detected by OCT in time.Compared with other methods for detecting brain edema, Scanning Source Optical Coherence Tomography (SS-OCT) is an ideal choice for basic research of ischemic brain edema, which can perform real-time high-resolution imaging in vivo.Therefore, it is likely to play an important role in the development of related drugs or the selection of treatment regimens[31].

4.3.3 Evaluation of collateral circulation

As for the collateral circulation of middle cerebral artery occlusion,some studies have shown that OCT imaging technology is used to examine the collateral circulation of middle cerebral artery occlusion.In related studies, the importance of the pia collateral circulation in the prevention of impending ischemic stroke is increasingly recognized, and the collateral circulation is also a major stimulusbased factor in the prevention of impending ischemic stroke.Doppler optical coherence tomography (DOCT) has been applied to spatiotemporal imaging of the MCA collateral circulation because it provides a powerful tool for quantifying in vivo blood flow parameters (velocity, flow, flow direction, and imaging path). The collateral circulation to the middle cerebral artery presents unique spatiotemporal dynamics in terms of its blood flow pattern and response to stimulation. DOCT technology can detect that sensory stimulation enhances blood flow parameters, which is beneficial to the monitoring, prevention and treatment of collateral circulation in clinical aortic ischemic stroke [32].

Studies on the response mechanism of OCT imaging technology after ischemic stroke have shown that protective reactions and related complications occur in the penumbra area around the infarction area after the occurrence of ischemic cerebral vessels. OCT imaging technology can well observe these post-stroke reaction mechanisms.Therefore, to judge the severity of these reaction mechanisms is conducive to improving the relevant treatment plan and prognosis.

5. Summary and prospect

Intracranial vascular disease is one of the major diseases that cause human disability and death for many years. At present,ischemic stroke is the most common intracranial vascular disease.For monitoring the etiology, pathogenesis and response mechanism of ischemic stroke, OCT imaging technology can make up for the deficiency of traditional imaging technology. It can comprehensively observe arterial stenosis and dissection, endothelial cells, thrombosis,vascular blood flow and perfusion, brain tissue repair and microvascular regeneration and function, brain collateral circulation after basilar artery thrombectomy.At the same time, OCT does not need contrast agent to avoid adverse reactions caused by contrast agent.In addition, OCT provides higher resolution, deeper insight into blood vessels, and faster angiography.However, it is worth noting that although OCT can accurately observe the structure and pathological characteristics of intracranial vessels, some vascular abnormalities may cause imaging quality deviation. At present,OCT imaging technology cannot completely replace the traditional imaging technology, but it still has better generalization and is expected to overcome the limitations of the existing technology.The OCT imaging after ischemic stroke etiology, mechanism, the reaction mechanism in animal and human, already has a part of the related research results, and constantly improve technology updates,hope OCT imaging technique in the treatment and prognosis of intracranial vascular diseases also have further study, finally makes the OCT imaging technology service in clinical use.

6. Author Contribution

First author: Xu Dingji: reading literature and writing paper;Corresponding author; Cai Yi: Project design and paper review;Other authors: Zhao Zhenqiang participated in literature collection.