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The ischemic penumbra was initially defined by Symon, Lassen and colleagues in the 1970s as an area of brain tissue with inadequate blood flow to maintain electric activity of neurons but adequate blood flow to preserve the function of the ion channels. This area of tissue, receiving enough blood to survive but not enough to function, often surrounds or abuts the irreversibly damaged core in ischemic stroke. It was shown that if blood flow could be restored to this area of marginal perfusion, the tissue could survive and function again, and growth of the core could be prevented. Based on seminal PET studies, penumbra or "penumbral tissue" eventually took on a subtly different meaning - the area of brain that is destined to progress to infarct unless blood flow is restored within a particular time window. The penumbra thus became the target for all acute stroke interventions - to preserve viability of the tissue and restore function. New imaging techniques, including diffusion and perfusion MRI and CT perfusion, were developed to rapidly identify individuals with penumbra, who were thought to be the best candidates for aggressive interventions to restore blood flow, particularly beyond the licensed time-window for IV thrombolysis. However, most clinical trials have failed to establish the usefulness of identifying candidates for treatment in this way using pre-specified protocols and primary endpoints. These trials have used different and sometimes unvalidated thresholds of hypoperfusion as well as irreversible infarct and various definitions of significant penumbra (or mismatch between irreversible infarct and hypoperfused, but salvageable tissue), and reanalysis of their data using more refined image processing showed post-hoc positivity. They have also evaluated outcome in a variety of ways, with few studies measuring the direct effect of restoring blood flow on the function of the penumbral tissue. Therefore, important remaining questions include how to define, characterize, and image the penumbra in acute stroke to achieve the greatest reliability and validity for what we want to measure, and whether this concept, so defined, provides an optimal target for stroke therapy using state-of-the-art trial design.

Acute ischemic stroke. --- Computer tomography perfusion. --- Penumbra. --- Cerebrovascular disease.

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The ischemic penumbra was initially defined by Symon, Lassen and colleagues in the 1970s as an area of brain tissue with inadequate blood flow to maintain electric activity of neurons but adequate blood flow to preserve the function of the ion channels. This area of tissue, receiving enough blood to survive but not enough to function, often surrounds or abuts the irreversibly damaged core in ischemic stroke. It was shown that if blood flow could be restored to this area of marginal perfusion, the tissue could survive and function again, and growth of the core could be prevented. Based on seminal PET studies, penumbra or "penumbral tissue" eventually took on a subtly different meaning - the area of brain that is destined to progress to infarct unless blood flow is restored within a particular time window. The penumbra thus became the target for all acute stroke interventions - to preserve viability of the tissue and restore function. New imaging techniques, including diffusion and perfusion MRI and CT perfusion, were developed to rapidly identify individuals with penumbra, who were thought to be the best candidates for aggressive interventions to restore blood flow, particularly beyond the licensed time-window for IV thrombolysis. However, most clinical trials have failed to establish the usefulness of identifying candidates for treatment in this way using pre-specified protocols and primary endpoints. These trials have used different and sometimes unvalidated thresholds of hypoperfusion as well as irreversible infarct and various definitions of significant penumbra (or mismatch between irreversible infarct and hypoperfused, but salvageable tissue), and reanalysis of their data using more refined image processing showed post-hoc positivity. They have also evaluated outcome in a variety of ways, with few studies measuring the direct effect of restoring blood flow on the function of the penumbral tissue. Therefore, important remaining questions include how to define, characterize, and image the penumbra in acute stroke to achieve the greatest reliability and validity for what we want to measure, and whether this concept, so defined, provides an optimal target for stroke therapy using state-of-the-art trial design.

Acute ischemic stroke. --- Computer tomography perfusion. --- Penumbra. --- Cerebrovascular disease.

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One in six suffers a stroke during their lifetime and stroke remains the major cause of new onset disability in adulthood. The worldwide burden of stroke is increasing due to an ageing population, however, globally haft of stroke victims are young. Stroke is the clinical diagnosis of an acute vascular incident and covers a multitude of pathophysiological causes. The clinician needs imaging to make decisions on acute treatment as well as to plan a secondary prevention strategy: a non-contrast CT and a Duplex of the carotids followed by an aspirin as a one size fits all strategy does not always provide sufficient support for those decisions. Presently, fast, generally available, and non-invasive imaging provides new possibilities of establishing a cause of stroke, provide specific information on the brain parenchyma – including possibly salvageable tissue and micro-bleeds – as well as allowing for more specific prognostication in acute stroke. This eBook covers both ischemic and haemorrhagic stroke and includes hot topics such as micro-bleeds, salvageable tissue and spot-sign, clinically challenging issues including movement artefacts in MRI as well as an overview of present options including pragmatic and feasible suggestions for an approach to state of the art acute imaging.

intracerebral hemorrage --- acute stroke --- cerebral amyloid angiopathy --- hemorrhagic stroke --- ischemic stroke --- spot-sign

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

non-invasive multimodal photonic diagnostics --- laser Doppler flowmetry --- NIRS --- optoacoustic technique --- ischemic stroke --- hemodynamics regulation

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

intracranial atherosclerosis --- endovascular treatment --- large vessel occlusion --- preventive treatment --- ischemic stroke