Unveiling the complexity of acute ischemic stroke through imaging and neuropathological insights

Effective management of acute ischemic stroke requires timely recanalization of occluded cerebral vessels, restoration of perfusion to the ischemic penumbra, and minimization of infarct volume. At present, clinicians rely heavily on various imaging modalities to evaluate the ischemic penumbra and core. However, the current imaging techniques often fail to accurately reflect the underlying cellular and histopathological changes associated with ischemia and lack standardized assessment criteria. This may lead to inconsistencies in diagnosis and treatment, ultimately compromising patient outcomes. Consequently, there is an urgent need to refine these imaging methods to better reflect the dynamic pathophysiology of cerebral ischemia. This review addresses these critical issues by first examining the shortcomings of current imaging approaches in assessing the ischemic penumbra and core. It highlights the discrepancies in these assessments and their implications for clinical practice. Furthermore, it proposes that integrating quantitative measures of salvageable ischemic regions with imaging-based molecular markers can enhance the precision of delineating the ischemic penumbra and core, thereby facilitating improved therapeutic decision-making. Finally, this review explores emerging biomarkers identified through the analysis of molecular and cellular mechanisms triggered by ischemia and hypoxia, underscoring their potential role in future diagnostics. Future imaging methods should strive to bridge the gap between microscopic cellular and molecular events and reliable imaging markers, ultimately enabling the identification of ischemic regions through biomarkers.