Hypersensitive Multiparametric MRA for Mild Traumatic Brain Injury: Simultaneous Imaging of Hemorrhagic Foci, Vascular Integrity, and Collaterals

Diagnosing mild traumatic brain injury (mTBI) remains a significant clinical challenge as many injuries are either invisible or difficult to detect with conventional medical imaging techniques. Here, an advanced multiparametric magnetic resonance angiography (MRA) strategy using biocompatible NaGdF₄ nanoparticles is proposed for precise mTBI diagnosis. The NaGdF₄ nanoparticles demonstrate excellent <i>T</i>₁ imaging performance due to their optimal hydrodynamic diameters and surface Gd³⁺ ions. Meanwhile, the intrinsic magnetism and magnetic anisotropy endow them with a significant <i>T</i>₂ effect and improving susceptibility-weighted imaging (SWI) capabilities. These properties enable the visualization of microvessels as small as 96 μm in 3D dynamic contrast-enhanced (DCE) imaging and 66 μm in SWI. In the context of mTBI diagnosis, the enhanced 3D DCE imaging allows for precise identification of microbleeding foci as small as 1.31 × 0.89 × 0.43 mm (<i>l</i> × <i>w</i> × <i>h</i>) and accurate localization relative to major blood vessels (e.g., 0.64 mm right of the superior sagittal sinus, 1.22 mm behind the rostral rhinal vein, 0.73 mm left of the anterior facial vein, and 0.45 mm deep from the scalp). Furthermore, the enhanced SWI technique sensitively detects regions with altered vascular permeability and clearly outlines enlarged collateral vessels surrounding the injury─features that are not visible in noncontrast-enhanced magnetic resonance imaging. Overall, this NaGdF₄-based multiparametric MRA method provides a highly sensitive and precise alternative to traditional imaging, significantly improving diagnostic accuracy and clinical utility in mTBI detection.