Prospective head motion correction at 3 Tesla with wireless NMR markers and ultrashort echo navigators.

PURPOSE: Prospective motion correction (PMC) with inductively-coupled wireless NMR markers has been shown to be an effective plug-and-play method for dealing with head motion at 7 Tesla [29,30]. However, technical challenges such as one-to-one identification of three wireless markers, generation of hyper-intense marker artifacts and low marker peak SNR in the navigators has limited the adoption of this technique. The goal of this work is to introduce solutions to overcome these issues and extend this technique to PMC for brain imaging at 3 Tesla. METHODS: PMC with 6 degrees of freedom (DOF) was implemented using a novel ∼8 ms, ultrashort echo time (UTE) navigator in concert with optimally chosen MnCl2 marker samples to minimize marker artifacts. Distinct head coil sensitivities were leveraged to enable identification and tracking of individual markers and a variable flip angle (VFA) scheme and real time filtering were used to boost marker SNR. PMC was performed in 3D T1 weighted brain imaging at 3 Tesla with voluntary head motions in adult volunteers. RESULTS: PMC with wireless markers improved image quality in 3D T1 weighted images in all subjects compared to non-motion corrected images for similar motions with no noticeable marker artifacts. Precision of motion tracking was found to be in the range of 0.01-0.06 mm/degrees. Navigator execution had minimal impact on sequence duration. CONCLUSIONS: Wireless NMR markers provide an accurate, calibration-free and economical option for 6 DOF PMC in brain imaging across field strengths. Challenges in this technique can be addressed by combining navigator design, sample selection and real time data processing strategies.

TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients.

BACKGROUND: Radical surgery is the first line treatment for localized prostate cancer (PC), however, several studies have demonstrated that surgical procedures induce tumor cell mobilization from the primary tumor into the bloodstream. METHODS: The number and temporal fluctuations of circulating tumor cells (CTC), cancer associated fibroblasts (CAF) and CTC cluster present in each blood sample was determined. RESULTS: The results show that both CTC and CTC cluster levels significantly increased immediately following primary tumor resection, but returned to baseline within 2 weeks post-surgery. In contrast, the CAF level decreased over time. In patients who experienced PC recurrence within months after resection, CTC, CAF, and cluster levels all increased over time. Based on this observation, we tested the efficacy of an experimental TNF-related apoptosis-inducing ligand (TRAIL)-based liposomal therapy ex-vivo to induce apoptosis in CTC in blood. The TRAIL-based therapy killed approximately 75% of single CTCs and CTC in cluster form. CONCLUSION: Collectively, these data indicate that CTC cluster and CAF levels can be used as a predictive biomarker for cancer recurrence. Moreover, for the first time, we demonstrate the efficacy of our TRAIL-based liposomal therapy to target and kill prostate CTC in primary patient blood samples, suggesting a potential new adjuvant therapy to use in combination with surgery.