When choosing an electromagnetic tracking system ͑EMTS͒ for image-guided procedures several factors must be taken into consideration. Among others these include the system's refresh rate, the number of sensors that need to be tracked, the size of the navigated region, the system interaction with the environment, whether the sensors can be embedded into the tools and provide the desired transformation data, and tracking accuracy and robustness. To date, the only factors that have been studied extensively are the accuracy and the susceptibility of EMTSs to distortions caused by ferromagnetic materials. In this paper the authors shift the focus from analysis of system accuracy and stability to the broader set of factors influencing the utility of EMTS in the clinical environment. The authors provide an analysis based on all of the factors specified above, as assessed in three clinical environments. They evaluate two commercial tracking systems, the Aurora system from Northern Digital Inc., and the 3D Guidance system with three different field generators from Ascension Technology Corp. The authors show that these systems are applicable to specific procedures and specific environments, but that currently, no single system configuration provides a comprehensive solution across procedures and environments.
Purpose: Immunotherapy promises unprecedented benefits to patients with cancer. However, the majority of cancer types, including high-risk neuroblastoma, remain immunologically unresponsive. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can mechanically fractionate tumors, transforming immunologically ''cold'' tumors into responsive ''hot'' tumors.Experimental Design: We treated <2% of tumor volume in previously unresponsive, large, refractory murine neuroblastoma tumors with mechanical HIFU and assessed systemic immune response using flow cytometry, ELISA, and gene sequencing. In addition, we combined this treatment with aCTLA-4 and aPD-L1 to study its effect on the immune response and long-term survival.Results: Combining HIFU with aCTLA-4 and aPD-L1 significantly enhances antitumor response, improving survival from 0% to 62.5%. HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL2, IFNg, and DAMPs, whereas immune regulators like CD4 þ Foxp3 þ , IL10, and VEGF-A are significantly reduced. HIFU combined with checkpoint inhibitors induced significant increases in intratumoral CD4 þ , CD8a þ , and CD8a þ CD11c þ cells, CD11c þ in regional lymph nodes, and decrease in circulating IL10 compared with untreated group. We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared with tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, P < 0.0001). This combination treatment significantly also induces CD4 þ CD44 þhi CD62L þlow and CD8a þ CD44 þhi CD62L þlow population and is adoptively transferable, imparting immunity, slowing subsequent de novo tumor engraftment.Conclusions: Mechanical fractionation of tumors using HIFU can effectively induce immune sensitization in a previously unresponsive murine neuroblastoma model and promises a novel yet efficacious immunoadjuvant modality to overcome therapeutic resistance.
We presented the first in vivo use of a complete system with stereoscopic AR visualization capability. This new capability introduces new visual cues and enhances visualization of the surgical anatomy. The system shows promise to improve the precision and expand the capacity of minimally invasive laparoscopic surgeries.
The goal of this work is to develop an innovative method that combines bioprinting and endoscopic imaging to repair tympanic membrane perforations (TMPs). TMPs are a serious health issue because they can lead to both conductive hearing loss and repeated otitis media. TMPs occur in 3-5% of cases after ear tube placement, as well as in cases of acute otitis media (the second most common infection in pediatrics), chronic otitis media with or without cholesteatoma, or as a result of barotrauma to the ear. About 55,000 tympanoplasties, the surgery performed to reconstruct TMPs, are performed every year, and the commonly used cartilage grafting technique has a success rate between 43% and 100%. This wide variability in successful tympanoplasty indicates that the current approach relies heavily on the skill of the surgeon to carve the shield graft into the shape of the TMP, which can be extremely difficult because of the perforation's irregular shape. To this end, we hypothesized that patient specific acellular grafts can be bioprinted to repair TMPs. In vitro data demonstrated that our approach resulted in excellent wound healing responses (e.g., cell invasion and proliferations) using our bioprinted gelatin methacrylate constructs. Based on these results, we then bioprinted customized acellular grafts to treat TMP based on endoscopic imaging of the perforation and demonstrated improved TMP healing in a chinchilla study. These ear graft techniques could transform clinical practice by eliminating the need for hand-carved grafts. To our knowledge, this is the first proof of concept of using bioprinting and endoscopic imaging to fabricate customized grafts to treat tissue perforations. This technology could be transferred to other medical pathologies and be used to rapidly scan internal organs such as intestines for microperforations, brain covering (Dura mater) for determination of sites of potential cerebrospinal fluid leaks, and vascular systems to determine arterial wall damage before aneurysm rupture in strokes.
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