Refining the Mismatch Concept in Acute Stroke: Lessons Learned from PET and MRI

Abstract

In ischemic stroke, positron-emission tomography (PET) established the imaging-based concept of penumbra. It defines hypoperfused, but functionally impaired, tissue with preserved viability that can be rescued by timely reperfusion. Diffusion-weighted and perfusion-weighted (PW) magnetic resonance imaging (MRI) translated the concept of penumbra to the concept of mismatch. However, the use of mismatch-based patient stratification for reperfusion therapy remains a matter of debate. The equivalence of mismatch and penumbra, as well as the validity of the classical mismatch concept is questioned for several reasons. First, methodological differences between PET and MRI lead to different definitions of the tissue at risk. Second, the mismatch concept is still poorly standardized among imaging facilities causing relevant variability in stroke research. Third, relevant conceptual issues (e.g., the choice of the adequate perfusion measure, the best quantitative approach to perfusion maps, and the required size of the mismatch) need further refinement. Fourth, the use of single thresholds does not account for the physiological heterogeneity of the penumbra and probabilistic approaches may be more promising. The implementation of this current knowledge into an optimized state-of-the-art mismatch model and its validation in clinical stroke studies remains a major challenge for future stroke research.

Early Identification of Potentially Salvageable Tissue with MRI-Based Predictive Algorithms after Experimental Ischemic Stroke

“…Dichotomization of MRIderived perfusion-and diffusion-based lesion volumes into overlapping and nonoverlapping areas enables selection of patients with a 'perfusion-diffusion mismatch' who may be eligible for thrombolytic treatment. 2,6,7 However, lack of standard postprocessing procedures and threshold values may compromise robust characterization of a 'perfusion-diffusion mismatch', 3,8 and volumetric analysis may obscure and oversimplify the complex and heterogeneous status of the affected tissue. 7,9,10 This mismatch area may therefore overestimate the actual tissue area at risk, 5,11,12 as well as exclude injured tissue that is potentially salvageable.…”

Lesion Development and Reperfusion Benefit in Relation to Vascular Occlusion Patterns after Embolic Stroke in Rats

“…A total of 73 rats (53 normotensive and 20 hypertensive animals) fulfilled the inclusion criteria, i.e., MRA and MRI within 2 hours, and acute ADC-and MTT-based lesion volumes larger than 1 mm 3 . Figure 1 shows examples of MR angiograms of rats' Circle of Willis with the absence of flow in the ipsilateral ICA, proximal (M1), and/or distal (M2) segments of the MCA acutely after intracarotid blood clot injection.…”

“…16 Collateral flow may not only prolong tissue salvageability, 3,19 it may also improve thrombolytic efficacy by providing additional delivery routes to the site of occlusion. 13 Despite the potential of the angiographydiffusion mismatch to aid in identifying tissue salvageability on reperfusion, it does not provide direct information on local perfusion or collateral flow.…”

“…13 Despite the potential of the angiographydiffusion mismatch to aid in identifying tissue salvageability on reperfusion, it does not provide direct information on local perfusion or collateral flow. 3,26 Additionally, MRA (especially timeof-flight MRA) has decreased sensitivity to flow in more distal parts of the arterial tree, which may lead to inexact assessment of the degree of arterial obstruction. 6 Future studies that include methods that enable quantitative measurement of collateral flow could significantly contribute to better understanding of the perfusion-diffusion mismatch and improved assessment of tissue salvageability after stroke.…”

“…However, the concept of the angiography-diffusion mismatch has been disputed as it may disregard possible compensatory mechanisms of collateral flow from other feeding arteries, and as such may overestimate tissue at risk of infarction. 3,5,6 The aims of the current study were to determine the relationship between ischemic lesion patterns and vascular occlusion profiles, and to compare the efficacy of the perfusion-diffusion and angiography-diffusion mismatch paradigms in predicting benefit from subsequent reperfusion. Our experimental study in which acute embolic stroke was induced in normotensive rats, and in spontaneously hypertensive rats (which have impaired collateral flow 7 ), allowed us to (1) correlate the development of acute ischemic lesions, as measured with DWI and PWI, with the pattern of flow obstruction in segments of the Circle of Willis, as measured with MRA, and (2) establish the sensitivity and specificity of the angiography-diffusion and perfusion-diffusion mismatch concepts to predict tissue salvageability on reperfusion.…”