Technical Note: Clinical translation of the Rapid-Steady-State-T1 MRI method for direct cerebral blood volume quantification.

PURPOSE: In preclinical studies, the Rapid-Steady-State-T1 (RSST1) MRI method has advantages over conventional MRI methods for blood volume fraction (BVf) mapping, since after contrast agent administration, the BVf is directly quantifiable from the signal amplitude corresponding to the vascular equilibrium magnetization. This study focuses on its clinical implementation and feasibility. METHODS: Following sequence implementation on clinical Philips Achieva scanners, the RSST1-method is assessed at 1.5 and 3 T in the follow-up examination of neurooncological patients receiving 0.1-0.2 mmol/kg Gd-DOTA to determine the threshold dose needed for cerebral BVf quantification. Confounding effects on BVf quantification such as transendothelial water exchange, transverse relaxation, and contrast agent extravasation are evaluated. RESULTS: For a dose≥0.13 mmol/kg at 1.5 T and ≥0.16 mmol/kg at 3 T, the RSST1-signal time course in macrovessels and brain tissue with Gd-DOTA impermeable vasculature reaches a steady state at maximum amplitude for about 8 s. In macrovessels, a BVf of 100% was obtained validating cerebral microvascular BVf quantification (3.5%-4.5% in gray matter and 1.5%-2.0% in white matter). In tumor tissue, a continuously increasing signal is detected, necessitating signal modeling for tumor BVf calculation. CONCLUSIONS: Using approved doses of Gd-DOTA, the steady state RSST1-signal in brain tissue is reached during the first pass and corresponds to the BVf. The first-pass duration is sufficient to allow accurate BVf quantification. The RSST1-method is appropriate for serial clinical studies since it allows fast and straightforward BVf quantification without arterial input function determination. This quantitative MRI method is particularly useful to assess the efficacy of antiangiogenic agents.

Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward tumor blood volume quantification without requiring the arterial input function.

PURPOSE: This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination. METHODS: For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase. We applied the mathematical model in a pilot-study on a RG2-glioma model to compare extravasation of two Gd-based CAs. The BVf quantification using the mathematical model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated using a ΔR2 *-steady-state MRI method with an USPIO and by immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye in the same rats. RESULTS: BVf in tumor and in healthy brain tissues (0.034 ± 0.005 and 0.026 ± 0.004, respectively) derived from the dynamic RSST1 signal were confirmed by ΔR2 *-steady-state MRI (0.036 ± 0.003 and 0.027 ± 0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036 ± 0.003 and 0.025 ± 0.004 respectively, rS = 0.87). CONCLUSION: Straightforward tumor BVf quantification without AIF determination is demonstrated in presence of CA leakage. The method will facilitate angiogenesis assessment in longitudinal neuro-oncologic studies in particular when monitoring the response to antiangiogenic therapies.