Limitations and Blind Spots of Diffusion-Weighted Imaging in the Evaluation of Acute Brain Ischemia: A Narrative Review

Diffusion-weighted imaging (DWI) has been increasingly utilized in the emergent evaluation of acute ischemic stroke (AIS). DWI enhances the sensitivity of diagnosis and enables the use of delayed reperfusion treatments in selected cases. However, DWI is not without limitations. DWI-negative AIS may be encountered in up to 1 out of 4 patients with minor stroke. We searched PubMed and Google Scholar for studies reporting on the prevalence of DWI-negative AIS from 2021 to 2025 and we extensively reviewed the relevant literature. Additionally, we included cases from our practice to highlight key points. DWI-negative AIS prevalence was 16% in one meta-analysis and ranged from 6,9% to 23,2% in identified studies that met our inclusion criteria. Biological, pathophysiological, technical, epidemiological and clinical factors that contribute to DWI-negative stroke are presented in detail. Overall, the application of diffusion imaging modalities in stroke is not bereft of blind spots despite enhanced sensitivity. Over-reliance on advanced neuroimaging and unfamiliarity with limitations predispose to errors in AIS assessment. Awareness about predisposing factors, treatment effect and prognosis guides appropriate decision-making, promoting good outcomes. Prospective appropriately-designed trials should address crucial issues such as the association between timing of imaging and DWI negativity.