UTE-ΔR₂-ΔR₂* combined MR whole-brain angiogram using dual-contrast superparamagnetic iron oxide nanoparticles

The ability to visualize whole-brain vasculature is important for quantitative in vivo investigation of vascular malfunctions in cerebral small vessel diseases, including cancer, stroke and neurodegeneration. Transverse relaxation-based ΔR₂ and ΔR₂* MR angiography (MRA) provides improved vessel-tissue contrast in animal deep brain with the aid of intravascular contrast agents; however, it is susceptible to orientation dependence, air-tissue interface artifacts and vessel size overestimation. Dual-mode MRA acquisition with superparamagnetic iron oxide nanoparticles (SPION) provides a unique opportunity to systematically compare and synergistically combine both longitudinal (R₁) and transverse (ΔR₂ and ΔR₂*) relaxation-based MRA. Through Monte Carlo (MC) simulation and MRA experiments in normal and tumor-bearing animals with intravascular SPION, we show that ultrashort TE (UTE) MRA acquires well-defined vascularization on the brain surface, minimizing air-tissue artifacts, and combined ΔR₂ and ΔR₂* MRA simultaneously improves the sensitivity to intracortical penetrating vessels and reduces vessel size overestimation. Consequently, UTE-ΔR₂-ΔR₂* combined MRA complements the shortcomings of individual angiograms and provides a strategy to synergistically merge longitudinal and transverse relaxation effects to generate more robust in vivo whole-brain micro-MRA.