Background and Purpose— Early neurological deterioration (END) is a relatively common unfavorable course after anterior circulation ischemic stroke that can lead to worse clinical outcome. None of the END predictors identified so far is sufficiently reliable to be used in clinical practice and the mechanisms underlying END are not fully understood. We review the evidence from the literature for a role of hemodynamic and perfusion abnormalities, more specifically infarction of the oligemia, in END. Summary of Review— After an overview of the neuroimaging, including perfusion imaging, predictors of END, we review the putative mechanisms of END with a special focus on hemodynamic factors. The evidence relating perfusion abnormalities to END is addressed and potential hemodynamic mechanisms are suggested. Conclusions— Hemodynamic factors and perfusion abnormalities are likely to play a critical role in END. Infarction of the oligemic tissue surrounding the penumbra could be the putative culprit leading to END as a result of perfusion, but also physiological and biochemical abnormalities. Further studies addressing the role of the oligemia in END and developing measures to protect its progression to infarction are now needed.

Background and Purpose— Nitroimidazole imaging is a promising contender for noninvasive in vivo mapping of brain hypoxia after stroke. However, there is a dearth of knowledge about the behavior of these compounds in the various pathophysiologic situations encountered in ischemic stroke. In this article we report the findings from a systematic review of the literature on the use of the nitroimidazoles to map hypoxia after stroke. Summary of Review— We describe the characteristics of nitroimidazoles as imaging tracers, their pharmacology, and results of both animal and clinical studies during and after focal cerebral ischemia. Findings in brain tumors are also presented to the extent that they enlighten results in stroke. Early results from application of kinetic modeling for quantitative measurement of tracer binding are briefly discussed. Conclusions— Based on this literature review, nitroimidazole hypoxia imaging agents are of considerable interest in stroke because they appear, both in animal models and in humans, to specifically detect the severely hypoxic viable tissue, but not the reperfused nor the necrotic tissue. To fully realize this potential in stroke, however, formal validation by concurrent measurement of tissue oxygen tension, together with development of novel ligands with faster distribution kinetics, faster clearance from normal tissue, and well-defined trapping mechanisms, are important goals for future investigations.

Background—: Cerebral infarcts distal to carotid stenoses are thought to be caused by emboli from inflamed, destabilized plaques. We hypothesized that microembolic signals (MES) on transcranial Doppler will be associated with carotid plaque inflammation on ¹⁸ F fluorodeoxyglucose positron-emission tomography (FDG PET) in recently symptomatic patients. Methods and Results—: Sixteen patients presenting with recent (47±31 days) anterior circulation transient ischemic attack or minor stroke and 50% to 99% stenosis of the ipsilateral carotid bifurcation underwent FDG PET, high-resolution black-blood carotid MRI, and transcranial Doppler for detection of MES. Patients with potential cardiac sources of emboli or contralateral MES were excluded. Regions of interest defined on the coregistered MRI were used to measure FDG standardized uptake values (with Rousset partial volume correction) from the index and contralateral carotid plaques and artery. Ipsilateral MES were detected in 7 patients (MES+ group) and absent in 8 (MES− group). There was a significant difference in index-to-contralateral plaque standardized uptake value ratio between MES+ (median, 1.05; first to third quartile, 0.96 to 1.32) and MES− (median, 0.76; first to third quartile, 0.62 to 0.94) patients ( P =0.005). The interval from symptom onset to PET and percent index carotid stenosis were not different between the 2 groups ( P =0.68 and P =0.48, respectively). Conclusions—: In this sample of recently symptomatic patients with carotid stenosis, an association was found between in vivo measures of plaque inflammation detected by FDG PET and the presence of transcranial Doppler MES. These findings strengthen the notion that embolic events distal to carotid stenoses are related to plaque inflammation, and FDG PET may be useful in the investigation of culprit carotid lesions.

Background and Purpose— Watershed ischemia is a significant cause of stroke in severe carotid disease, but its pathophysiology is unsettled. Although hemodynamic compromise has long been regarded as the main mechanism—particularly with deep watershed infarction—there is some contradictory evidence from clinical and pathological studies for a role of microembolism, thought to result from plaque inflammation. However, no study so far has directly addressed these conflicting scenarios. Methods— In 16 consecutive patients with recent transient ischemic attack/minor stroke and ipsilateral 50% to 99% carotid stenosis, we prospectively obtained (1) plaque inflammation mapping with ¹⁸ F fluorodeoxyglucose positron emission tomography; (2) brain MRI and perfusion MR; and (3) transcranial Doppler detection of microembolic signals (MES). Patients were excluded if on dual antiplatelets or with a potential cardiac source of emboli or contralateral MES. Results— We found the expected significant relationship between (1) degree of stenosis and severity of distal hemodynamic impairment in the watershed areas; and (2) degree of in vivo plaque inflammation and rate of MES/hr. Deep watershed infarcts were present in 8 patients and MES in 8 (3 with both). There was no systematic association between the presence of deep watershed infarcts and either hemodynamic impairment or MES, but deep watershed infarcts were present only when either hemodynamic impairment or MES was present ( P =0.01). Conclusion— This pilot study supports the idea that in symptomatic carotid disease, deep watershed infarcts result either from hemodynamic impairment secondary to severe lumen stenosis or from microembolism secondary to plaque inflammation. There was no direct evidence that both mechanisms act in synergy.