Max Planck Institute for Neurological Research, Cologne, Germany.
Int J Stroke. 2010 Aug;5(4):290-5. doi: 10.1111/j.1747-4949.2010.00444.x.
The 'penumbra' is a concept coined in animal experiments suggesting that functionally impaired tissue can survive and recover if sufficient reperfusion is re-established within a limited time period, which depends on the level of residual flow. In an ischaemic territory, irreversible damage progresses over time from the centre of the most severe flow reduction to the periphery with less disturbed perfusion. This centrifugal progression of irreversible tissue damage is characterised by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusion disturbances. Waves of depolarisations, the peri infarct spreading depressions, inducing activation of ion pumps and liberation of excitatory transmitters play an important role in the drastically increased metabolic demand during reduced oxygen supply causing hypoxic tissue changes and lactacidosis, which further damage the tissue. Positron emission tomography allows the quantification of regional cerebral blood flow, the regional metabolic rate for oxygen and the regional oxygen extraction fraction, which can be used to identify regions with a critical reduction in these physiologic variables as indicators of penumbra and irreversible damage within ischaemic territories in animal models and patients with stroke. These positron emission tomography methods require arterial blood sampling and due to the complex logistics involved, are limited for routine application. Therefore, newer tracers were developed for the noninvasive detection of irreversible tissue damage (flumazenil) and of hypoxic tissue changes (fluoromisonidazole). As a widely applicable clinical tool, diffusion/perfusion-weighted magnetic resonance imaging is used; the 'mismatch' between perfusion and diffusion changes serves as a surrogate marker of the penumbra. However, in comparative studies of magnetic resonance imaging and positron emission tomography, diffusion-weighted imaging showed a high false-positive rate of irreversible damage, and the perfusion-weighted-diffusion-weighted mismatch overestimated the penumbra as defined by positron emission tomography. Advanced analytical procedures of magnetic resonance imaging data may improve the reliability of these surrogate markers but should be validated with quantitative procedures.
“半影”是一个在动物实验中提出的概念，表明在有限的时间内，如果重新建立足够的再灌注，功能受损的组织可以存活并恢复，如果剩余流量的水平。在缺血区域，随着时间的推移，从最严重的血流减少的中心到灌注较少受干扰的外围，不可逆损伤会逐渐进展。这种不可逆组织损伤的离心进展以复杂的级联相互关联的电生理、分子、代谢和灌注紊乱为特征。去极化波，即梗死周围扩散性抑制，诱导离子泵的激活和兴奋性递质的释放，在氧供应减少时代谢需求急剧增加中起着重要作用，导致缺氧组织变化和乳酸性酸中毒，进一步损伤组织。正电子发射断层扫描允许量化局部脑血流、局部氧代谢率和局部氧提取分数，这些可以用来识别这些生理变量临界减少的区域，作为动物模型和中风患者缺血区域内半影和不可逆损伤的指标。这些正电子发射断层扫描方法需要动脉采血，并且由于涉及到复杂的物流，因此限制了常规应用。因此，为了非侵入性检测不可逆组织损伤（氟马西尼）和缺氧组织变化（氟米索硝唑），开发了新的示踪剂。作为一种广泛应用的临床工具，弥散/灌注加权磁共振成像被用于；灌注和弥散变化之间的“不匹配”作为半影的替代标志物。然而，在磁共振成像和正电子发射断层扫描的比较研究中，弥散加权成像显示不可逆损伤的假阳性率较高，而灌注加权-弥散加权不匹配高估了正电子发射断层扫描定义的半影。磁共振成像数据的高级分析程序可以提高这些替代标志物的可靠性，但应通过定量程序进行验证。
