Defining the Ischemic Penumbra Using Hyperacute Neuroimaging: Deriving Quantitative Ischemic Thresholds

Abstract

Despite three decades of promise, a neuro-imaging 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.

Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal

“…However, the assumption that the diffusion lesion represents the core whereas abnormalities visible in certain perfusion weighted images include both the core and the penumbra is still applied in many studies (Ford et al, 2012; James et al, 2006; Petrella and Provenzale, 2000). Nevertheless, there is still an ambiguity surrounding the definition of the penumbra using thresholds (Ford et al, 2012). In Fig.…”

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

“…A static perfusion deficit does not capture the dynamic response to ischemia known to occur at the molecular level (18). Thus, when making decisions about costly and potentially harmful interventions for the treatment of acute stroke, perfusion imaging can be misleading, resulting in higher morbidity and mortality rates due to in appropriate interventions (17, 62–64). However, when impaired perfusion is significant enough to affect metabolism, a systemic intracellular acidosis ensues propagating out from a central infarct core, sparing regions of oligemia that have not resulted in anaerobic metabolism.…”

Editorial

“…The lack of underlying biological justification for choosing different threshold values discerning DWI/PWI mismatch (and CT perfusion) is also partially addressed by Ford et al [33] who propose to directly image the "ischemic penumbra." Specifically, they point out that the measurements of the cerebral metabolic rate of oxygen utilization may allow the identification of ischemic penumbra in vivo.…”

“…Ford et al [33] also address the issue of the best data analysis scheme to allow the determination of imaging threshold values for ischemic core, penumbra, and oligemia. Specifically, unlike the past and current ongoing studies using DWI/PWI where patients are grouped into either with or without the presence of targeted mismatch, Ford et al [33] suggest a tissue-based analysis approach.…”

“…Specifically, unlike the past and current ongoing studies using DWI/PWI where patients are grouped into either with or without the presence of targeted mismatch, Ford et al [33] suggest a tissue-based analysis approach. Using a threeimaging time point design, at baseline, immediately after tPA, and 1-3 month follow-up, the imaging data could offer a means to separate brain tissues into different categories based on the presence or absence of reperfusion after treatment and the final fate of the tissues (Table 1 in Ford et al) which in turn allow experimental derivation of imaging threshold for ischemic core, penumbra, and oligemia.…”