Clinical Imaging of the Penumbra in Ischemic Stroke: From the Concept to the Era of Mechanical Thrombectomy

Abstract

The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O2. Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions.

DWI-FLAIR Mismatch in Stroke: “P.S.” (Partial Strategic Concept) for Clinical Practice

“…Others have also looked at the apparent diffusion coefficient (ADC) value as a threshold for reversibility, following revascularization with values ranging between 0.52 × 10 −3 and 0.62 × 10 −3 mm 2 /s. 6,7 In our patients, ADC values within the infarcts varied between 0.18 × 10 −3 and 0.64 × 10 −3 mm 2 /s. They did not differ between the mismatch and nonmismatch areas.…”

Advances in cerebral perfusion imaging techniques in acute ischemic stroke

“…If the occluded artery is not revascularized promptly, the penumbra may progress to irreversible infarction 8 . Hence, timely reperfusion therapy is the most effective maneuver for rescuing the penumbra and preventing infarct core growth in patients with AIS 9,10 …”

“…Moreover, two clinical trials, DAWN and DEFUSE‐3, provided evidence for the benefits of revascularization treatment in patients with LAO in an extended time window of up to 24 h after the time at which they were last known to be well, which is effectively based on perfusion imaging criteria for patient selection using computed tomography (CT) perfusion or magnetic resonance imaging (MRI) 17,18 . As a result, a paradigm for selecting patients with AIS to receive reperfusion treatment has shifted from a “time‐based” to a “tissue‐based” approach, using perfusion imaging to establish a more flexible and individualized therapeutic window according to the patients' unique pathophysiologic status; this has the potential to optimize patient selection and increase the proportion of patients who are amenable to treatment 10,19 …”

“…17,18 As a result, a paradigm for selecting patients with AIS to receive reperfusion treatment has shifted from a "time-based" to a "tissue-based" approach, using perfusion imaging to establish a more flexible and individualized therapeutic window according to the patients' unique pathophysiologic status; this has the potential to optimize patient selection and increase the proportion of patients who are amenable to treatment. 10,19 Currently, perfusion imaging based on CT or MRI is used as a routine evaluation of AIS in emergent settings to provide clinicians with rapid and quantitative image-based evidence about the infarct core and penumbra to help them select eligible patients to receive reperfusion treatment. 20,21 However, the time required to transport patients to CT or MR imaging extends door-to-reperfusion time.…”

Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches

“…Nowadays, clinical diagnosis of IS mainly relies on magnetic resonance imaging and computed tomography [ 4 ]. However, most community medical institutions lack the testing equipment, and the brain imaging examinations are relatively expensive, which limits the clinical diagnosis of IS [ 5 ]. Thus, developing new diagnostic markers and therapeutic targets for IS are urgently needed.…”