Functional Hemodynamic Assessment in Intracranial Atherosclerotic Disease: From Anatomical Stenosis to μQFR-Guided Precision Medicine.

Abstract

Intracranial atherosclerotic stenosis (ICAS) is the leading cause of ischemic stroke worldwide, especially in Asians. Current risk stratification depends mainly on the degree of anatomical narrowness. Growing evidence indicates a significant separation between lumen stenosis and lesion-specific hemodynamic impairment. This phenomenon highlights the limitations of anatomy-based assessment alone. In this context, researchers began to adopt a physiologically oriented assessment strategy. This strategy is seen as a promising approach to improve individualized ICAS diagnosis and guide treatment decision-making. The Murray's law-based quantitative flow ratio (μQFR) is a novel angiography-derived functional index that enables rapid, wire-free, and nonhyperemic assessment of translesional hemodynamic impairment using digital subtraction angiography (DSA). Originally translated from coronary functional imaging, the μQFR has recently been adapted for intracranial circulation evaluation and has shown strong agreement with invasive pressure-derived indices. Emerging studies further reveal that the μQFR is correlated with downstream cerebral hypoperfusion, ischemic injury on diffusion-weighted imaging (DWI), collateral circulation status, and long-term cerebrovascular outcomes. In this review, we summarize the technical principles underlying the μQFR; critically evaluate the current evidence supporting its validation and prognostic value in ICAS; and discuss its relationship with invasive physiology, cerebral perfusion imaging, collateral compensation, and computational flow modeling. We further propose that the μQFR should not be viewed merely as an alternative to anatomical stenosis grading but rather as part of integrated cerebrovascular physiology-guided precision treatment. Overall, the μQFR represents a promising step toward functional hemodynamic stratification in ICAS and may serve as a practical biomarker linking focal stenotic physiology to tissue-level ischemic vulnerability.