Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and has few effective treatment options. A previous study suggested that pretreatment MRI may be helpful in identifying patients likely to benefit from hepatic arterial infusion pump therapy with floxuridine (HAI-FUDR) (1). The purpose of this prospective study was to investigate the ability of pre-treatment and early post treatment DCE- and DWI-MRI to predict response in a phase 2 trial of combination HAI-FUDR and systemic chemotherapy with gemcitabine/oxaliplatin (GemOx) for patients with unresectable ICC.18 consecutive patients were recruited for this institutional review board approved prospective study between January 2013 and August 2015. Scans were performed at 1.5T (G.E. Signa 450, Waukeshau, WI). DCE-MRI and DWI were performed before and after treatment (1 month of HAI-FUDR and 2 weeks of GemOx). 2 patients were excluded, one with an incomplete MRI data set, one with a single tumor that was too small for analysis. 3 patients did not meet the 3 month follow-up period for response assessment. For DCE-MRI a free-breathing, 3D-fat-saturated FLASH sequence was prescribed in the oblique coronal plane (matrix 256x128, FOV 340-440, slice thickness = 5-7 mm TE = 1.5 ms, TR = 4.2 ms, flip angle 30°, temporal resolution = 6-8s). Images were prescribed over the largest tumor and Gd-BOPTA at 0.1 mmol/kg was injected at 2 ml/sec. For DWI an oblique coronal single-shot EPI sequence was used (matrix 128x128, FOV 340-440 mm, slice thickness 5-7 mm, TE = 68 ms, TR ~4s b values = 0, 50, 250, 350, 500 s/mm2). K^trans was calculated following QIBA guidelines2. An average pre-contrast tumor T1 value was calculated based on data from 5 patients. An average AIF was modeled based on Parker, et. al.3 using data from an aortic ROI in 8 patients. In the extended Tofts’s model a single-input vascular function was utilized under the assumption that ~80% of tumor supply was arterial. ADC was calculated by monoexponential fit using all b values. Response (% change in sum of diameter) was measured after 3 months and 6 months of treatment by RECIST 1.1 on follow-up MRI. We estimated the rank correlation between K^trans and ADC at baseline, as well as change from baseline, and response at 1, 3 and 6 months. In a supplementary analysis we dichotomized response and estimated the area under the ROC curve for each of the imaging parameters at baseline and change from baseline.At the time of analysis, 13 patients (3 males, 10 females, median age 66 years old) had measurable response at 3 months post treatment and 9 patients had measurable response at 6 months. Mean tumor ADC and median K^trans are discussed herein. Baseline ADC was positively correlated with % change in sum of diameters (%ΔSD) at 3 and 6 months (p < 0.005 and p < 0.05, respectively), while baseline K^trans appeared to be inversely related to %ΔSD but this was not significant (Figs 1a-d). ΔADC at 1 month was negatively correlated with %ΔSD at 3 months (p < 0.001) but was not significant for 6 month %ΔSD, while the change in K^trans at 1 month follow-up was not correlated with %ΔSD at 3 or 6 months (Figs 2a-d). 3 patients had a partial response (PR) at 3 months (>30% %ΔSD reduction) and 6 patients had PR at 6 months. Figure 3 contains the areas under the receiver operator characteristic curves for baseline and Δparameter values for predicting PR at 3 and 6 months. Baseline ADC and ΔADC (BL-1MO) were the strongest predictors of PR.Our preliminary analysis shows the potential of multimodality MRI, in particular, DW-MRI, to predict response of unresectable ICC to combination HAI-FUDR and systemic chemotherapy using MRI acquired at baseline or early in treatment (1 month follow-up). Tumors with lower ADC at baseline and larger increases in ADC after 1 month of therapy had the greatest response, possibly reflecting initial high cellularity and development of necrosis after therapy, respectively. When the trial completes patient accrual, we will extend the analysis to include the value of combining K^trans and ADC.