Introduction: Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. Methods: Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (Ktrans, ve, kep, and vp). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P < 0.05. Results: mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5 mm (3.0). ROI volume was 278 mm3 (222). ADC was 1.07 (0.27) × 10–3 mm2/s. DCE metrics were Ktrans 0.085/min (0.063), ve 0.060 (0.052), kep 1.20/min (0.32), and vp 1.48 % (0.82). Patients with >33 % monosomy 3 had higher Ktrans and higher ve values than those with disomy 3 or ≤33 % monosomy (P < 0.01). There were no significant differences between ADC (P = 0.07), kep (P = 0.37), and vp with respect to monosomy 3. Conclusion: mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma.

G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (δORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and β-arrestin 1 (β-arr1) to regulate actin polymerization. This controls receptor function,as assessed by agonist-induced inhibition of voltage-dependent Ca2+channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and β-arr1. Functional evidence of this cascade was demonstrated invivo, where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function