Radiotherapy Assessment Using Diffusion Weighted MRI

Purpose: There are two goals of this study. The first goal of this study is to investigate the feasibility of using classic textural feature extraction in radiotherapy response assessment among a unique cohort of early stage breast cancer patients who received the single-dose preoperative radiotherapy. The second goal of this study is to investigate the clinical feasibility of using classic texture features as potential biomarkers which are supplementary to regional apparent diffusion coefficient in gynecological cancer radiotherapy response assessment.

Methods and Materials: For the breast cancer study, 15 patients with early stage breast cancer were enrolled in this retrospective study. Each patient received a single-fraction radiation treatment, and DWI and DCE-MRI scans were conducted before and after the radiotherapy. DWI scans were acquired using a spin-echo EPI sequence with diffusion weighting factors of b = 0 and b = 500 mm2/s, and the apparent diffusion coefficient (ADC) maps were calculated. DCE-MRI scans were acquired using a T1-weighted 3D SPGR sequence with a temporal resolution of about 1 minute. The contrast agent (CA) was intravenously injected with a 0.1 mmol/kg bodyweight dose at 2 ml/s. Two parameters, volume transfer constant (Ktrans) and kep were analyzed using the two-compartment Tofts pharmacokinetic model. For pharmacokinetic parametric maps and ADC maps, 33 textural features were generated from the clinical target volume (CTV) in a 3D fashion using the classic gray level co-occurrence matrix (GLCOM) and gray level run length matrix (GLRLM). Wilcoxon signed-rank test was used to determine the significance of each texture feature’s change after the radiotherapy. The significance was set to 0.05 with Bonferroni correction.

For the gynecological cancer study, 12 female patients with gynecologic cancer treated with fractionated external beam radiotherapy (EBRT) combined with high dose rate (HDR) intracavitary brachytherapy were studied. Each patient first received EBRT treatment followed by five fractions of HDR treatment. Before EBRT and before each fraction of brachytherapy, Diffusion Weighted MRI (DWI-MRI) and CT scans were acquired. DWI scans were acquired in sagittal plane utilizing a spin-echo echo-planar imaging sequence with weighting factors of b = 500 s/mm2 and b = 1000 s/mm2, one set of images of b = 0 s/mm2 were also acquired. ADC maps were calculated using linear least-square fitting method. Distributed diffusion coefficient (DDC) maps and stretching parameter α were calculated. For ADC and DDC maps, 33 classic texture features were generated utilizing the classic gray level run length matrix (GLRLM) and gray level co-occurrence matrix (GLCOM) from high-risk clinical target volume (HR-CTV). Wilcoxon signed-rank statistics test was applied to determine the significance of each feature’s numerical value change after radiotherapy. Significance level was set to 0.05 with multi-comparison correction if applicable.

Results: For the breast cancer study, regarding ADC maps calculated from DWI-MRI, 24 out of 33 CTV features changed significantly after the radiotherapy. For DCE-MRI pharmacokinetic parameters, all 33 CTV features of Ktrans and 33 features of kep changed significantly.

For the gynecological cancer study, regarding ADC maps, 28 out of 33 HR-CTV texture features showed significant changes after the EBRT treatment. 28 out of 33 HR-CTV texture features indicated significant changes after HDR treatments. The texture features that indicated significant changes after HDR treatments are the same as those after EBRT treatment. 28 out of 33 HR-CTV texture features showed significant changes after whole radiotherapy treatment process. The texture features that indicated significant changes for the whole treatment process are the same as those after HDR treatments.

Conclusion: Initial results indicate that certain classic texture features are sensitive to radiation-induced changes. Classic texture features with significant numerical changes can be used in monitoring radiotherapy effect. This might suggest that certain texture features might be used as biomarkers which are supplementary to ADC and DDC for assessment of radiotherapy response in breast cancer and gynecological cancer.

On the Regulation of Small Actors: Three Experimental Essays about Policies based on Voluntary Compliance and Decentralized Monitoring

Monitoring and enforcement are perhaps the biggest challenges in the design and implementation of environmental policies in developing countries where the actions of many small informal actors cause significant impacts on the ecosystem services and where the transaction costs for the state to regulate them could be enormous. This dissertation studies the potential of innovative institutions based on decentralized coordination and enforcement to induce better environmental outcomes. Such policies have in common that the state plays the role of providing the incentives for organization but the process of compliance happens through decentralized agreements, trust building, signaling and monitoring. I draw from the literatures in collective action, common-pool resources, game-theory and non-point source pollution to develop the instruments proposed here. To test the different conditions in which such policies could be implemented I designed two field-experiments that I conducted with small-scale gold miners in the Colombian Pacific and with users and providers of ecosystem services in the states of Veracruz, Quintana Roo and Yucatan in Mexico. This dissertation is organized in three essays.

The first essay, “Collective Incentives for Cleaner Small-Scale Gold Mining on the Frontier: Experimental Tests of Compliance with Group Incentives given Limited State Monitoring”, examines whether collective incentives, i.e. incentives provided to a group conditional on collective compliance, could “outsource” the required local monitoring, i.e. induce group interactions that extend the reach of the state that can observe only aggregate consequences in the context of small-scale gold mining. I employed a framed field-lab experiment in which the miners make decisions regarding mining intensity. The state sets a collective target for an environmental outcome, verifies compliance and provides a group reward for compliance which is split equally among members. Since the target set by the state transforms the situation into a coordination game, outcomes depend on expectations of what others will do. I conducted this experiment with 640 participants in a mining region of the Colombian Pacific and I examine different levels of policy severity and their ordering. The findings of the experiment suggest that such instruments can induce compliance but this regulation involves tradeoffs. For most severe targets – with rewards just above costs – raise gains if successful but can collapse rapidly and completely. In terms of group interactions, better outcomes are found when severity initially is lower suggesting learning.

The second essay, “Collective Compliance can be Efficient and Inequitable: Impacts of Leaders among Small-Scale Gold Miners in Colombia”, explores the channels through which communication help groups to coordinate in presence of collective incentives and whether the reached solutions are equitable or not. Also in the context of small-scale gold mining in the Colombian Pacific, I test the effect of communication in compliance with a collective environmental target. The results suggest that communication, as expected, helps to solve coordination challenges but still some groups reach agreements involving unequal outcomes. By examining the agreements that took place in each group, I observe that the main coordination mechanism was the presence of leaders that help other group members to clarify the situation. Interestingly, leaders not only helped groups to reach efficiency but also played a key role in equity by defining how the costs of compliance would be distributed among group members.

The third essay, “Creating Local PES Institutions and Increasing Impacts of PES in Mexico: A real-Time Watershed-Level Framed Field Experiment on Coordination and Conditionality”, considers the creation of a local payments for ecosystem services (PES) mechanism as an assurance game that requires the coordination between two groups of participants: upstream and downstream. Based on this assurance interaction, I explore the effect of allowing peer-sanctions on upstream behavior in the functioning of the mechanism. This field-lab experiment was implemented in three real cases of the Mexican Fondos Concurrentes (matching funds) program in the states of Veracruz, Quintana Roo and Yucatan, where 240 real users and 240 real providers of hydrological services were recruited and interacted with each other in real time. The experimental results suggest that initial trust-game behaviors align with participants’ perceptions and predicts baseline giving in assurance game. For upstream providers, i.e. those who get sanctioned, the threat and the use of sanctions increase contributions. Downstream users contribute less when offered the option to sanction – as if that option signal an uncooperative upstream – then the contributions rise in line with the complementarity in payments of the assurance game.

Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical.

In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications.

We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the distribution of dipoles in a given sample of chromophore constructs. The model can be used to evaluate the feasibility of other potential orientation control techniques.