[ISC2015]侧支循环评估及影像学检查在脑血管病中的应用 ——加州大学洛杉矶分校David S. Liebeskind教授专访
编者按:神经影像学的重要性在脑血管疾病的管理中不言而喻。2015国际卒中大会(ISC)上,大量采用各种神经影像技术的研究展示。加州大学洛杉矶分校神经科神经血管成像研究中心David S. Liebeskind教授在本届大会上也呈现了数项研究数据。据此,《国际循环》记者在现场对其进行了采访。
《国际循环》:对急性卒中患者的管理,侧支循环对于患者的预后非常重要。目前临床研究中最常用的侧支血管评估方法是什么?侧支循环和再灌注如何决定组织损伤的?
International Circulation: Collaterals are vital for the management of acute stroke patients. What are the most commonly used methods for evaluating collaterals in clinical studies? How do collaterals and reperfusion determine tissue injury?
Liebeskind教授:侧支循环是机体通过其他血管输送血流从而对抗低灌注或缺血性损伤的机制。评估侧支血管的方法有很多,通常我们可通过血管造影对具体侧支血管进行测量。但随时间推移,各种成像技术不断进步,我们发现很多其他标志物如侧支灌注和灌注不匹配等可间接反映侧支循环状态,几乎所有影像学研究中,急性卒中患者的侧支血流均更好,而非更差。多项试验已显示对侧支循环分析与评估非常有用,这为我们应用影像学方法选择患者干预带来了很大信心。这非常重要,因为我们需选择特定患者干预。因此,对急性卒中患者行临床评估后,需进一步通过影像学评估其侧支循环情况。
Dr Liebeskind: Collateral circulation is the mechanism that the body has to offset hypoperfusion or ischemic injury by routing blood flow through other vessels. Collaterals are measured differently. Traditionally, they have been measured by way of an angiogram looking at the very specific collateral vessels. But with advances in various imaging techniques over time, there are other correlates or associated markers which give an indirect reflection of collateral status, whether it is collateral perfusion, perfusion mismatch and other measures. On almost any imaging study, there are correlates or associates of better collateral flow as opposed to worse collateral flow. What we have seen in various trials is that these analyses of collateral circulation have actually been very potent and given us tremendous faith in the use of imaging to select patients for intervention. That is important because we want to select certain patients for intervention and you do want to exclude other patients. So the imaging of collateral circulation is the next step following the clinical evaluation of any acute stroke patient.
《国际循环》:支架取栓时代,侧支循环分级如何决定脑缺血再灌注时间?
International Circulation: How does collateral grade drive the importance of time to reperfusion in the stentriever era?
Liebeskind教授:我们对脑缺血再灌注时间给予大量关注。但我认为专业知识有助于我们每个人进步更快,应用影像学技术评估侧支循环是非常专业的领域,需要让每个人都了解。在欧洲的德国和奥地利多家中心开展的ENDOSTROKE注册登记研究显示,侧支循环与缺血再灌注时间的关系非常复杂,因此对侧支循环进行分级有重要意义。侧支循环较差的患者恶化速度非常快,因此留给我们对其干预时间可能非常短,可能有些患者侧支循环太差,以至于无法接受治疗。另一方面,有些患者侧支循环非常好,时间对其来说相对不太重要,但我们还需尽快对其救治,如同我们治疗卒中注重时效性一样。如果患者侧支循环情况较好,可采用包括在相对较晚时间窗内开展血管内治疗等多种措施。问题的关键在于我们必须通过影像学或血管造影评估侧支循环状态。因此,最关键时段可能是从发病至影像学检查时间。影像学检查到再灌注所需时间很大程度上取决于影像学所见。此外,我想强调的是,人们经常忘记影像学检查的目的是什么,影像学检查不仅仅为了成像,而是需根据成像结果对特定患者行个体化治疗,预测卒中结局及病情随时间的变化。
Dr Liebeskind: We focus tremendous on time and how long it takes to do things, but I think everyone knows that expertise will allow you to go faster and the use of imaging to explore collateral flow is a field of expertise which is important to educate everyone about. Being able to grade collaterals is important because what we have seen in the ENDOSTROKE registry that was performed in Europe many different centers in Germany and Austria is that the relationship between collaterals and time is complex. Patients with poor collaterals can worsen very quickly and therefore your time to intervene might be very short. There are some patients with such poor collateral flow that you may exclude them from therapy all together. At the other extreme, you have patients with robust or good collaterals, and in those patients, time is less relevant. You still want to go as fast as you can but you may have more time, which is important in terms of the implications of how we treat stroke in general. There may be more patients we can treat with various therapies including endovascular therapies at later time windows if we understand that they have good collaterals. The twist is that you have to evaluate collateral status; you have to get to that point with imaging or angiography to understand that. Therefore, the most critical time period is probably the time to imaging. From imaging onward depends on what you see on that imaging. The other point I would make is that people often forget what we do with imaging. It is not just time to imaging and then just move on. You have to use imaging for the value that it brings in understanding the specific stroke case in front of you and what it is likely to tell you about stroke outcome and how the patient is going to do over time.
《国际循环》:灌注成像在颅内动脉粥样硬化疾病管理中的作用是什么?
International Circulation: What about the role of perfusion imaging in the management of intracranial atherosclerotic disease?
Liebeskind教授:亚洲人群中颅内动脉粥样硬化性疾病更多见,且与美国等西方国家相比,前者低灌注及各种灌注变化的管理存在很大差异。在西方,鉴于颅内动脉粥样硬化性疾病较少见,一般情况下,我们首先认定患者为急性血栓性闭塞,而不会先考虑患者基线或既往是否存在灌注问题或灌注不足区域。在亚洲,情况则不同。各中心研究小组发现,颅内动脉粥样硬化性疾病时大脑各区域存在灌注延迟,但患者却可完全无症状,即使检测半暗带风险的标志,使用时间指标即PWI的达峰时间(Tmax),发现会出现Tmax延迟现象。缺失的部分是血容量。当患者水合状态或容量状态等发生变化时,血容量会迅速改变,出现明显灌注异常;一旦上述情况恢复,灌注异常不再显著。因此,采用多参数方法对了解灌注不同组分及确定病情进展非常重要。不同人群的颅内动脉硬化性疾病发病存在显著差异。颅内动脉粥样硬化性疾病较多见国家人群的卒中发生率相对较低,原因在于其存在对抗潜在低灌注状态的较好的侧支循环。这种情况下,颅内动脉粥样硬化性疾病所致卒中通常仅在灌注瞬时崩溃时发作。
Dr Liebeskind: This is highly applicable and a real issue in Asia where there is a lot more intracranial atherosclerotic disease. The management of hypoperfusion and various perfusion changes is actually quite different than what it is in the United States or elsewhere in the Western hemisphere. In the West, we assume everything is an acute embolic occlusion basically because we see very few cases of intracranial atherosclerotic disease. We don’t expect that anyone would have a baseline or pre-existing perfusion problem or region of hypoperfusion. This is not the case in Asia. We have seen this and other groups from different centers have shown this nicely that with intracranial atherosclerotic disease, you can have a delay in perfusion to various locations of the brain and be completely asymptomatic. Even when measured with a marker of penumbral risk, Tmax as a time parameter, the Tmax delay can be present. The missing piece is the blood volume. When patients change their hydration status or volume status or anything else and blood volume changes rapidly, all of a sudden perfusion becomes much more significant. Once it is restored, the perfusion abnormality is not as significant again. So this multi-parametric approach of understanding the different components of perfusion is very important as well as looking at what happens over time. The size of strokes in these two different populations are radically different. The average stroke is around ten times smaller in countries which see intracranial atherosclerotic disease compared to others. The reason is that there has been good collateral flow that has been built up over time to offset the potential hypoperfusion. The strokes that then occur are only transient collapses in perfusion when due to the mechanism of intracranial atherosclerotic disease.
《国际循环》:动脉自旋MRI如何量化急性到亚急性卒中患者脑血流随血压的改变?
International Circulation: How dose arterial spin labeled MRI quantify cerebral blood flow changes with blood pressure from acute to subacute stroke?
Liebeskind教授:目前,大家都非常关注血压并意识到其对急性卒中患者的重要性,血压是可测量的最基本指标。尽管如此,出血性及缺血性卒中的血压管理尚存争议。我们知道,高血压是卒中患者预后较差的标志。当患者出现缺血性卒中时,我们通常并不仔细询问或考虑患者血压变化原因,而是一味地试图改变血压。至少在美国,人们常认为通过降压药降低血压血压,有助于脑血流量恢复。亚急性卒中患者动脉自旋MRI研究显示,血压水平与血流量呈负相关。这虽听起来有悖常理,但血压高于某一水平时,血压越高,脑血流量确实会降低。原因与血流到达这些区域所经血管及方式有关。一般情况下,全身血液动力学发生变化时,机体可通过自调节限制到达某些区域的血流量。缺血性卒中亚急性期时,机体某些部分自调节会受影响,但未受影响区域仍具备完整自调节功能。因此,若患者血压较高或在ICU行升压治疗时,可能会导致血管收缩及与之矛盾的脑血流量减少。
Dr Liebeskind: Everyone is fascinated by blood pressure and what it means in an acute stroke patient because it is one of the most basic things you can measure in patients. Despite that, in hemorrhage and ischemic stroke, there is still debate as to what to do about it. We know that when it is high, it is a marker, in general, of a worse outcome. We often don’t ask why at the time so we move forward by trying to change the blood pressure and when the patient has an ischemic stroke, then, at least in the United States, pressure medications are used to boost the pressure with the idea that you can restore blood flow via this technique. When we looked at arterial spin labeled perfusion MRI studies in stroke patients during the subacute phase, we noticed an inverse correlation between the blood pressure level and blood flow. It sounds counterintuitive but with the blood pressure higher at a point in time, the blood flow in the brain is lower. Why does this occur? It all has to do with the plumbing and the way that the blood flow is reaching these areas. In general, autoregulation is able to restrict the amount of blood flow into a territory in response to changes in systemic hemodynamics. In ischemic stroke in the subacute phase, there are changes to autoregulation, but the unaffected territories have intact autoregulation and as a result, when you have a higher blood pressure or push pressure higher in the ICU, there may be vasoconstriction and the paradoxical effect of a decrease in the amount of blood flow.