Three-dimensional, in-silico breast phantom for multimodality image simulations

We report on the construction of anatomically realistic three-dimensional in-silico breast phantoms with adjustable sizes, shapes and morphologic features. The concept of multiscale spatial resolution is implemented for generating breast tissue images from multiple modalities. Breast epidermal boundary and subcutaneous fat layer is generated by fitting an ellipsoid and 2nd degree polynomials to reconstructive surgical data and ultrasound imaging data. Intraglandular fat is simulated by randomly distributing and orienting adipose ellipsoids within a fibrous region immediately within the dermal layer. Cooper’s ligaments are simulated as fibrous ellipsoidal shells distributed within the subcutaneous fat layer. Individual ductal lobes are simulated following a random binary tree model which is generated based upon probabilistic branching conditions described by ramification matrices, as originally proposed by Bakic et al [3, 4]. The complete ductal structure of the breast is simulated from multiple lobes that extend from the base of the nipple and branch towards the chest wall. As lobe branching progresses, branches are reduced in height and radius and terminal branches are capped with spherical lobular clusters. Biophysical parameters are mapped onto the complete anatomical model and synthetic multimodal images (Mammography, Ultrasound, CT) are generated for phantoms of different adipose percentages (40%, 50%, 60%, and 70%) and are analytically compared with clinical examples. Results demonstrate that the in-silico breast phantom has applications in imaging performance evaluation and, specifically, great utility for solving image registration issues in multimodality imaging.

Bioanalytical applications of microfluidic devices

The first part of the thesis describes a new patterning technique--microfluidic contact printing--that combines several of the desirable aspects of microcontact printing and microfluidic patterning and addresses some of their important limitations through the integration of a track-etched polycarbonate (PCTE) membrane. Using this technique, biomolecules (e.g., peptides, polysaccharides, and proteins) were printed in high fidelity on a receptor modified polyacrylamide hydrogel substrate. The patterns obtained can be controlled through modifications of channel design and secondary programming via selective membrane wetting. The protocols support the printing of multiple reagents without registration steps and fast recycle times. The second part describes a non-enzymatic, isothermal method to discriminate single nucleotide polymorphisms (SNPs). SNP discrimination using alkaline dehybridization has long been neglected because the pH range in which thermodynamic discrimination can be done is quite narrow. We found, however, that SNPs can be discriminated by the kinetic differences exhibited in the dehybridization of PM and MM DNA duplexes in an alkaline solution using fluorescence microscopy. We combined this method with multifunctional encoded hydrogel particle array (fabricated by stop-flow lithography) to achieve fast kinetics and high versatility. This approach may serve as an effective alternative to temperature-based method for analyzing unamplified genomic DNA in point-of-care diagnostic.

Paths to peace: conflict management trajectories in militarized interstate disputes

When multiple third-parties (states, coalitions, and international organizations) intervene in the same conflict, do their efforts inform one another? Anecdotal evidence suggests such a possibility, but research to date has not attempted to model this interdependence directly. The current project breaks with that tradition. In particular, it proposes three competing explanations of how previous intervention efforts affect current intervention decisions: a cost model (and a variant on it, a limited commitments model), a learning model, and a random model. After using a series of Markov transition (regime-switching) models to evaluate conflict management behavior within militarized interstate disputes in the 1946-2001 period, this study concludes that third-party intervention efforts inform one another. More specifically, third-parties examine previous efforts and balance their desire to manage conflict with their need to minimize intervention costs (the cost and limited commitments models). As a result, third-parties intervene regularly using verbal pleas and mediation, but rely significantly less frequently on legal, administrative, or peace operations strategies. This empirical threshold to the intervention costs that third-parties are willing to bear has strong theoretical foundations and holds across different time periods and third-party actors. Furthermore, the analysis indicates that the first third-party to intervene in a conflict is most likely to use a strategy designed to help the disputants work toward a resolution of their dispute. After this initial intervention, the level of third-party involvement declines and often devolves into a series of verbal pleas for peace. Such findings cumulatively suggest that disputants hold the key to effective conflict management. If the disputants adopt and maintain an extreme bargaining position or fail to encourage third-parties to accept greater intervention costs, their dispute will receive little more than verbal pleas for negotiations and peace.