Defining the Ischemic Penumbra Using Hyperacute Neuroimaging: Deriving Quantitative Ischemic Thresholds
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REVIEW
Defining the Ischemic Penumbra Using Hyperacute Neuroimaging: Deriving Quantitative Ischemic Thresholds Andria L. Ford & Hongyu An & Katie D. Vo & Weili Lin & Jin-Moo Lee
Received: 12 March 2012 / Revised: 5 April 2012 / Accepted: 17 April 2012 / Published online: 1 May 2012 # Springer Science+Business Media, LLC 2012
Abstract Despite three decades of promise, a neuroimaging biomarker capable of delineating the ischemic penumbra is yet to be definitively demonstrated. Much progress has been made, especially with MR imaging. However, in order to rigorously define an imaging biomarker of the ischemic penumbra, carefully designed studies which can derive ischemic thresholds using quantitative imaging parameters may be required. Two thresholds are of interest: one which distinguishes the ischemic core from penumbra, and another which distinguishes the penumbra from benign oligemia. In this review, we discuss one possible approach to define these thresholds by following tissue fate in the presence or absence of early reperfusion. Keywords Acute ischemic stroke . Reperfusion . Magnetic resonance imaging . MRI . Neuroimaging . Threshold . Ischemic penumbra A. L. Ford : J.-M. Lee (*) Department of Neurology, Washington University, School of Medicine, 600 South Euclid Avenue, Campus Box 8111, Saint Louis, MO 63110, USA e-mail: [email protected] H. An : W. Lin Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA K. D. Vo : J.-M. Lee Department of Radiology, Washington University, School of Medicine, Saint Louis, MO, USA
The Ischemic Penumbra: from Concept to Clinical Practice The concept of the “ischemic penumbra,” first coined by Astrup in 1977, was based on almost a decade of research in a variety of gyrencephalic animal models of focal cerebral ischemia. These studies revealed two cerebral blood flow (CBF) thresholds of ischemia: an upper threshold which defined electrical failure in brain tissue, encompassing functionally impaired but structurally intact neurons (which corresponded to a CBF of 15 ml/100 g/min); and a lower threshold below which intracellular potassium was released into the extracellular space, which was believed to represent functional and structural impairment (corresponding to 6 ml/ 100 g/min) [1–3]. Astrup posed that the penumbra represented tissue between these two thresholds, including “areas with less severe ischemia…with electrical failure but sustained energy metabolism and low extracellular potassium and with the possible potential for recovery,” in contrast to the ischemic core which he described as “areas of severe ischemia with energy failure, high extracellular potassium, and developing infarction” [4]. This technical definition of penumbra was later generalized and rewritten as “a zone of nonfunctioning but still viable tissue that may recover its function if blood flow can be restored, for example, by therapeutic intervention.” [5], and has been widely accepted today. Critical to this definition was the concept that ischemic brain tissue c
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