Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition

Intravascular superparamagnetic iron oxide nanoparticles (SPION)-enhanced MR transverse relaxation rates (∆R2(⁎) and ∆R2) are widely used to investigate in vivo vascular parameters, such as the cerebral blood volume (CBV), microvascular volume (MVV), and mean vessel size index (mVSI, ∆R2(⁎)/∆R2). Although highly efficient, regional comparison of vascular parameters acquired using gradient-echo based ∆R2(⁎) is hampered by its high sensitivity to magnetic field perturbations arising from air-tissue interfaces and large vessels. To minimize such demerits, we took advantage of the dual contrast property of SPION and both theoretically and experimentally verified the direct benefit of replacing gradient-echo based ∆R2(⁎) measurement with ultra-short echo time (UTE)-based ∆R1 contrast to generate the robust CBV and mVSI maps. The UTE acquisition minimized the local measurement errors from susceptibility perturbations and enabled dose-independent CBV measurement using the vessel/tissue ∆R1 ratio, while independent spin-echo acquisition enabled simultaneous ∆R2 measurement and mVSI calculation of the cortex, cerebellum, and olfactory bulb, which are animal brain regions typified by significant susceptibility-associated measurement errors.