R.A. Omary, J. Deng, T.K. Rhee, F.H. Miller, M.F. Mulcahy, L. Kulik, R. Salem, A.C. Larson; Chicago/US

Purpose
Yttrium-90 radioembolization is a promising treatment for unresectable hepatocellular carcinoma (HCC). Median tumor response time for ⁹⁰Y therapy using traditional anatomic imaging is nearly 3 months. A functional imaging method that predicts HCC response to ⁹⁰Y therapy earlier would be welcome. Recent studies have demonstrated that diffusion-weighted MRI (DW-MRI) may predict treatment response in brain tumors and breast metastases, and is also useful to assess HCC response following chemoembolization. However, no studies have monitored DW-MRI changes in HCC after ⁹⁰Y radioembolization. We tested the hypothesis that functional DW-MRI can detect increased water diffusion in HCC following ⁹⁰Y therapy.

Material and methods
In this prospective study, we performed ⁹⁰Y radioembolization (TheraSphere, MDS Nordion, Kanata, ON, Canada) in 9 patients with HCC. For each patient, anatomic and functional DW-MRI were obtained before and ~40 days after 90Y therapy using a Sonata 1.5T clinical MR scanner (Siemens, Erlangen, Germany). Anatomic MRI consisted of T2-weighted and contrast-enhanced T1-weighted sequences, in the arterial and venous phases. Functional DW-MRI used single-shot spin-echo EPI with scan parameters: TR/TE = 2500/82 ms, slice thickness/gap = 8/4mm. partial Fourier factor = 6/8, non-selective fat saturation, twice refocused spin-echo diffusion weighting to reduce eddy-current induced distortion with b=0 and 500 s/mm^2. Apparent diffusion coefficient (ADC) maps were reconstructed from each series of DW images and used to measure mean tumor ADC values. We statistically compared mean tumor ADC values before and after ⁹⁰Y radioembolization using a matched pair t-test, with α = 0.05.

Results
Contrast-enhanced T1-weighted images typically showed peripheral enhancement corresponding to viable regions of HCC pre and post therapy. On DW-MRI, responsive tumors showed regions of low water mobility within the viable periphery (dark outer rim in ADC map), while the core of the tumor demonstrated increased water mobility corresponding to necrosis. Tumor conspicuity was relatively poor in most T2-weighted images with no significant changes in signal intensity following therapy. Tumor ADC increased significantly following ⁹⁰Y radioembolization. Pre-treatment mean (±SD) ADC was 1.37±0.22 x 10^-3 and post-treatment mean ADC was 2.03±0.31 x 10^-3 mm²/s, corresponding to a post-therapy mean tumor ADC increase of 0.66±0.38 x 10^-3 mm²/s (p=0.001). Two patients who did not respond to therapy showed smaller mean increases in ADC of 0.31 x 10^-3 mm²/s.

Conclusion
DW-MRI successfully detects increased water diffusion following ⁹⁰Y radioembolization, potentially earlier than conventional anatomic MRI changes. Future studies are necessary to a) correlate the time course of ADC changes in HCC with radioembolization response and b) verify if DWI can be used to predict future tumor response.