Development and Optimization of 19F-MRI for Tracking Cellular Therapeutics

Introduction: This thesis aims to advance magnetic resonance imaging (MRI) for imaging cellular therapeutics. Traditional, proton-based, MRI provides detailed anatomical images, particularly of soft tissue. However, in order to obtain information at a cellular level specialized imaging agents are required to detect the cells of interest. Perfluorocarbons containing non-radioactive fluorine-19 (19F) are both biologically safe and MR sensitive. Methods: Pre-clinical 19F-MRI was implemented on a Varian 9.4T MRI scanner, using a dual 19F/1H-tuned birdcage volume coil. Mesenchymal stromal cells (MSC) were pre-labeled with a commercial, FDA approved 19F-perfluorocarbon emulsion, then implanted intramuscularly into the mouse hindlimb. To track the inflammation resulting from transplantation, a dual-agent cellular MRI technique was developed. This technique utilizes 19F to track MSC and superparamagnetic iron oxide nanoparticles (SPIO) to image macrophages, through the presence of signal quenching. A clinical imaging protocol was developed to translate 19F-MRI on a 3T GE MR750 scanner with a dual 19F/1H-tuned surface coil. Peripheral blood mononuclear cells (PBMC) were labeled with a FDA-approved 19F-agent and injected into a ham shank phantom for protocol optimization. Results: The balanced steady-state free precession pulse sequence was chosen for all studies due to the high signal-to-noise per unit time. Image acquisition was optimized for 19F detection sensitivity, accuracy of quantification, and compatibility with isoflurane. In vivo quantification of MSC on the day of implantation was in strong agreement with the expected number of cells. The change in 19F-signal was quantified over time and compared between two murine transplantation models. When iron oxide was administered i.v., the migration of immune cells could be tracked to the injection site. The presence of SPIO decreased both the 1H and 19F signal, indicating that transplant rejection was occurring. On a clinical system, as few as 4x106 PBMC could be imaged following both surface and subcutaneous injection. The minimum number of detectable cells was strongly influenced by intracellular 19F uptake. Conclusions: 19F-MRI is a promising tool for imaging cellular therapeutics. By pre-labeling cells of interest, they can be localized and the change in signal can be quantified over time. The technique shows promise for both pre-clinical and clinical applications

Si nanocrystal synthesis via double implantation and variable implantation

Silicon (Si) nanocrystals (nc) precipitated from silicon-implanted silicon oxide (SiO2) are of interest as a novel light source for illumination, biomedical applications, optical computing, etc. They have some advantages over conventional III-V compound semiconductor nanocrystals produced by colloidal synthesis. They are compatible with Si/SiO2 based semiconductor processing, are stable, non-toxic at point of synthesis and consumption, and their luminescence falls with the infrared transmission window of biological materials. Unfortunately, synthesis of Si-nc embedded SiO2 is uneconomical and is not as amenable to precise control of the size distribution of nanocrystals as is the case for III-V compound colloidal nanocrystals. The distribution of nanocrystals precipitated out of a sample is affected by the purity of the SiO2 implantation target, the implantation temperature, the implanted Si+ dose and energy, the anneal temperature, the anneal ramp rate, total anneal time, and the use of secondary annealing in a passivating gas atmosphere. Two studies were conducted within the scope of this thesis. The first concerned the enhancement of Si-nc precipitation by use of a double implant procedure to increase the vacancy concentration in the implanted region. The second involved the development of a combinatorial implantation and characterization procedure to allow many implantation doses to be synthesized at once, thereby more rapidly optimizing synthesis procedure. An exponential dose profile was implanted in thermal oxide and fused silica. Optical absorption profiles were measured for the implanted fused silica and photoluminescence profiles were made for both samples. It was determined that the implanted thermal oxide yielded Si-nc with a quantum confinement mechanism. Both samples also yielded luminescence from another, unspecified mechanism. By comparing the quantum confined luminescence from the thermal oxide in both studies, it was confirmed that the double implant procedure does yield enhanced Si-nc precipitation, even with a much lower concentration of excess Si. Based on the literature review and experimental results, various recommendations are made for future work

Can Neuroscience Help Predict Future Antisocial Behavior?

Part I of this Article reviews the tools currently available to predict antisocial behavior. Part II discusses legal precedent regarding the use of, and challenges to, various prediction methods. Part III introduces recent neuroscience work in this area and reviews two studies that have successfully used neuroimaging techniques to predict recidivism. Part IV discusses some criticisms that are commonly levied against the various prediction methods and highlights the disparity between the attitudes of the scientific and legal communities toward risk assessment generally and neuroscience specifically. Lastly, Part V explains why neuroscience methods will likely continue to help inform and, ideally, improve the tools we use to help assess, understand, and predict human behavior

Alien Registration- Gaudet, Antoinette M. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24556/thumbnail.jp

Alien Registration- Gaudet, Antoinette M. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24556/thumbnail.jp

Daubert on the Brain: How New Mexico’s Daubert Standard Should Inform its Handling of Neuroimaging Evidence

Part I of this article reviews the expert evidence admissibility standard set forth in Daubert v. Merrell Dow Pharm., Inc. and New Mexico’s adoption of the Daubert standard in State v. Alberico.2 Part II of the article provides a summary of the framework expressed in the 2014 publication Group to Individual (G2i) Inference in Scientific Expert Testimony.3 Part III explores case law where DNA testing was considered as evidence and why the courts have concluded that DNA evidence complies with Daubert/Alberico standards. Part IV provides a summary of the use of euroimaging evidence in court and provides an overview of the different neuroimaging techniques being used. Neuroimaging evidence is being increasingly offered in both criminal and civil cases and as a result we believe that a basic familiarity with the different types of techniques is important for all jurists. Part V highlights the distinction between novel science and clinically-established science in showing that Daubert finds its highest purpose when evaluating novel techniques and theories. Part VI concludes that certain types of neuroscience data can be and has been deemed reliable at both the general and individual level through the application of Daubert under a G2i framework