The purpose of this pilot study was to evaluate acute tumor vasculature changes in hepatocellular carcinoma (HCC) using dynamic contrast enhanced MRI (DCE-MRI) following stereotactic body radiation therapy (SBRT). Patients with unresectable HCC based on multiphase imaging and treated with SBRT were eligible. Patients were required to have Child-Turcotte-Pugh A/B liver disease with 1-3 lesions amenable to SBRT with a tumor size ≤ 15 cm (single lesion or sum of lesions). A baseline MRI was performed within 2 weeks prior to the first fraction of SBRT. SBRT was delivered using a 2 or 3 arc volumetric arc therapy plan with 6 or 10 MV photons with a dose of 7.5 Gy. Following SBRT, post-treatment imaging was performed by either 6 or 24 hours after the first fraction. All research MRI scans were performed with a 3T whole-body MRI. DCE-MRI was performed with 60 dynamic cycles at a temporal resolution of 6 seconds. Contrast infusion (Gadobenate, 0.5 mL/sec) was initiated at the 10th dynamic cycle. DCE-MRI data were analyzed with the modified Brix’s pharmacokinetic model. The uni-directional exchange rate constants kep (interstitial space to blood plasma) and kpe (blood plasma to interstitial space) were reported as measures of vascular permeability/perfusion. Statistical analysis was performed using the Wilcoxon rank sum test. Eight patients (7 male/1 female) were enrolled with a median age of 65 years (range 48-79). Ten tumors were evaluated and treated with a median tumor size of 5.9 cm (range 1.6-12 cm). Five patients (7 tumors) completed post-treatment imaging between 20-24 hours post-SBRT while the remaining 3 patients (3 tumors) completed post-SBRT imaging 2-6 hours after treatment. Pharmacokinetic analysis of DCE-MRI revealed significant changes in tumor permeability/perfusion after a single fraction of SBRT. The exchange rate kpe showed a rapid increase within 6 hours post-SBRT (median 1005%, range 115∼1030%) followed by a subsequent decrease by 24 hours (median -24%, range -75∼17%, P=0.02). A similar trend was also observed for kep. However, it was of smaller magnitude and did not reach statistical significance (an initial increase in the 6-hour time window: median 105%, range -50∼218%; and a subsequent return to near baseline by 24 hours post-treatment: median 1%, range -29∼155%; P=0.7). Our preliminary results suggest that SBRT may trigger a rapid increase in tumor permeability/perfusion within 6 hours of radiation therapy delivery. The magnitude of this effect is subsequently diminished or reversed by 24 hours post-treatment. This 6-hour time window may provide an opportunity for better accessibility and efficacy when delivering chemotherapy or molecularly targeted agents in conjunction with moderate SBRT doses.