Intravoxel incoherent motion (IVIM) DW-MRI has demonstrated promise in simultaneously characterizing the properties of tumor diffusion and perfusion in cancer patients ^{1, 2} . Dynamic contrast enhanced (DCE)-MRI provides information of tumor vascularity and permeability ^{3, 4}. There is growing evidence that MRI perfusion can improve the diagnosis and prognosis of patients with brain tumors over conventional imaging alone ^{5, 6}. In the clinical settings it is essential to accurately assess, whether or not a brain metastasis has been successfully treated or whether the metastasis requires additional treatment. There are a currently a number of challenging issues that arise when attempting to accurately assess the treatment response of a brain metastasis treated by focal, high dose radiation therapy, such as stereotactic radiosurgery (SRS). Hence, it is essential to develop noninvasive quantitative imaging methods that will be able to determine if a metastasis has been successfully treated early in the patient’s treatment course. The purpose of this study was to determine whether quantitative imaging metrics derived from IVIM DW- and DCE- MRI can assess early treatment response in patients with brain metastases treated with SRS.Our institutional review board approved this prospective imaging study of patients with brain metastases treated with SRS. All patients signed informed consent. Brain metastases from any pathology were accepted. Patients had 1 pre- treatment (TX) and 1 post TX MRI [1-72 hours] for early response assessment. All MRIs were performed on a 3-T scanner (Ingenia; Philips Healthcare). IVIM DW-MRI acquisitions were performed using SS-EPI sequence (TR = 4000 ms, TE = 98-104 ms, NEX = 2, FOV (cm): 24, slice thickness (mm)= 5 with10 b values of b = 0, 20, 50, 80, 200, 300, 500, 800, 1500, 2000 s/mm2. DCE-MRI data acquisition: 3D-SPGR pulse sequence with 4 flip angles (FA=20, 80, 160, 300) was used for native T1 mapping, followed by dynamic imaging with contrast agent administration (FA=30o, TR = 4.6 ms, TE = 2.4 ms, phases = 40-60, NEX = 1, FOV (cm): 24, slice thickness (mm) =5). The contrast agent Gd-DTPA was delivered by antecubital vein catheters at a bolus of 0.1 mmol/kg and 2 cc/s, followed by saline flush. The regions of interest (ROIs) on the brain metastases were defined by an experienced neuro-radiologist, the apparent diffusion coefficients (ADC) as well as f (vascular fraction), D (pure diffusion coefficient), D* (pseudo-diffusion coefficient) were calculated by using monoexponential and biexponential functions with a scheme of noise correction respectively ⁷. A simplified two compartment standard model (SM) was used to analyze the data. The metrics derived from SM were K^trans (volume transfer constant), v_e (volume fraction of extravascular extracellular space),vp (volume fraction of vascular space). Clinical overall response was assessed as standard of care. Non-parametric Spearman correlation coefficients were calculated to investigate the correlation between the metrics and clinical response which was grouped as no evidence of disease (NED), alive with disease (AWD), dead of disease (DOD) and dead due to unknown reason (DUK).For the 5 patients, the brain metastases were analyzed using the 5 pre-Tx and 5 post-Tx MRIs. The post-Tx MRI was acquired within 72 hours of SRS to capture early treatment response. There was a significant association between the mean of the pre-treatment K^trans and ve (p=0.016) and the mean of the post-treatment Ktrans and v_e (p=0.032). On clinical follow up the survival status of patients was as follows: 2 AWD, 2 DOD and 1 DUK. Only D, Ktrans and ve metric maps for pre-, and post-treatment MRIs from a representative brain metastasis patient with AWD is shown in Figure 1 (Table 1). Similar metric maps are displayed for a brain metastasis patient who was DOD in Figure 2 (Table 1). Both the figures show promising and encouraging trends for AWD and DOD with metric values changing between pre- and post-treatment MRI which was soon after (within 72 hrs) SRS.We have demonstrated for the first time that perfusion and diffusion metric values can change substantially even within 72 hours post SRS. This is a key finding that may help treating physicians assess response very early on in the course of treatment and help in individualized patient management.Our study demonstrates promising early response results for patients with brain metastases undergoing SRS. These findings need to be validated in a larger patient population.