Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury. Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue. Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma. Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.

Surface guided radiation therapy (SGRT) is increasingly being adopted for use in radiation treatment delivery for Head and Neck (H&N) cancer patients. This study investigated the improvement of patient setup accuracy and reduction of setup time for SGRT compared to a conventional setup. A total of 60 H&N cancer patients were retrospectively included. Patients were categorized into three groups: oral cavity, oropharynx and nasopharynx/sinonasal sites with 20 patients in each group. They were further separated into two (2) subgroups, depending on whether they were set up with the aid of SGRT. The Align-RT™ system was used for SGRT in this work. Positioning was confirmed by daily kV-kV imaging in conjunction with weekly CBCT scans. Translational and rotational couch shifts along with patient setup times were recorded. Imaging setup time, which was defined as the elapsed time from the acquisition of the first image set to the end of the last image set, was recorded. Average translational shifts were larger in the non-SGRT group. Vertical shifts showed the most significant reduction in the SGRT group for both oropharynx and oral cavity groups. Pitch corrections were significantly higher in the SGRT group for oropharynx patients and higher pitch corrections were also observed in the SGRT groups of oral cavity and nasopharynx/sinonasal patients. The average setup time when SGRT guidance was employed was shorter for all three treatment sites although this did not reach statistical significance. The largest time reduction between the SGRT and non-SGRT groups was seen in the nasopharynx/sinonasal group. This study suggests that the use of SGRT decreases the magnitude of translational couch shifts during patient setup. However, the rotational corrections needed were generally higher with SGRT group. When SGRT was employed, a definite reduction in patient setup time was observed for nasopharynx/sinonasal and hypopharynx cancer patients.