Image reconstruction in fluorescence molecular tomography with sparsity-initialized maximum-likelihood expectation maximization

We present a reconstruction method involving maximum-likelihood expectation maximization (MLEM) to model Poisson noise as applied to fluorescence molecular tomography (FMT). MLEM is initialized with the output from a sparse reconstruction-based approach, which performs truncated singular value decomposition-based preconditioning followed by fast iterative shrinkage-thresholding algorithm (FISTA) to enforce sparsity. The motivation for this approach is that sparsity information could be accounted for within the initialization, while MLEM would accurately model Poisson noise in the FMT system. Simulation experiments show the proposed method significantly improves images qualitatively and quantitatively. The method results in over 20 times faster convergence compared to uniformly initialized MLEM and improves robustness to noise compared to pure sparse reconstruction. We also theoretically justify the ability of the proposed approach to reduce noise in the background region compared to pure sparse reconstruction. Overall, these results provide strong evidence to model Poisson noise in FMT reconstruction and for application of the proposed reconstruction framework to FMT imaging

Incorporating reflection boundary conditions in the Neumann series radiative transport equation: Application to photon propagation and reconstruction in diffuse optical imaging

We propose a formalism to incorporate boundary conditions in a Neumann-series-based radiative transport equation. The formalism accurately models the reflection of photons at the tissue-external medium interface using Fresnel’s equations. The formalism was used to develop a gradient descent-based image reconstruction technique. The proposed methods were implemented for 3D diffuse optical imaging. In computational studies, it was observed that the average root-mean-square error (RMSE) for the output images and the estimated absorption coefficients reduced by 38% and 84%, respectively, when the reflection boundary conditions were incorporated. These results demonstrate the importance of incorporating boundary conditions that model the reflection of photons at the tissue-external medium interface

Genomic Analysis of Chemo-Resistance to HDAC inhibitor in Gastric Cancer cells

Ph.DDOCTOR OF PHILOSOPH

Improved Modeling and Image Generation for Fluorescence Molecular Tomography (FMT) and Positron Emission Tomography (PET)

In this thesis, we aim to improve quantitative medical imaging with advanced image generation algorithms. We focus on two specific imaging modalities: fluorescence molecular tomography (FMT) and positron emission tomography (PET). For FMT, we present a novel photon propagation model for its forward model, and in addition, we propose and investigate a reconstruction algorithm for its inverse problem. In the first part, we develop a novel Neumann-series-based radiative transfer equation (RTE) that incorporates reflection boundary conditions in the model. In addition, we propose a novel reconstruction technique for diffuse optical imaging that incorporates this Neumann-series-based RTE as forward model. The proposed model is assessed using a simulated 3D diffuse optical imaging setup, and the results demonstrate the importance of considering photon reflection at boundaries when performing photon propagation modeling. In the second part, we propose a statistical reconstruction algorithm for FMT. The algorithm is based on sparsity-initialized maximum-likelihood expectation maximization (MLEM), taking into account the Poisson nature of data in FMT and the sparse nature of images. The proposed method is compared with a pure sparse reconstruction method as well as a uniform-initialized MLEM reconstruction method. Results indicate the proposed method is more robust to noise and shows improved qualitative and quantitative performance. For PET, we present an MRI-guided partial volume correction algorithm for brain imaging, aiming to recover qualitative and quantitative loss due to the limited resolution of PET system, while keeping image noise at a low level. The proposed method is based on an iterative deconvolution model with regularization using parallel level sets. A non-smooth optimization algorithm is developed so that the proposed method can be feasibly applied for 3D images and avoid additional blurring caused by conventional smooth optimization process. We evaluate the proposed method using both simulation data and in vivo human data collected from the Baltimore Longitudinal Study of Aging (BLSA). Our proposed method is shown to generate images with reduced noise and improved structure details, as well as increased number of statistically significant voxels in study of aging. Results demonstrate our method has promise to provide superior performance in clinical imaging scenarios

Proteomic analysis of HCC-M and HEPG2 cells after treatment by butyrate

Master'sMASTER OF SCIENC

More than Classification: A Unified Framework for Event Temporal Relation Extraction

Event temporal relation extraction~(ETRE) is usually formulated as a multi-label classification task, where each type of relation is simply treated as a one-hot label. This formulation ignores the meaning of relations and wipes out their intrinsic dependency. After examining the relation definitions in various ETRE tasks, we observe that all relations can be interpreted using the start and end time points of events. For example, relation \textit{Includes} could be interpreted as event 1 starting no later than event 2 and ending no earlier than event 2. In this paper, we propose a unified event temporal relation extraction framework, which transforms temporal relations into logical expressions of time points and completes the ETRE by predicting the relations between certain time point pairs. Experiments on TB-Dense and MATRES show significant improvements over a strong baseline and outperform the state-of-the-art model by 0.3\% on both datasets. By representing all relations in a unified framework, we can leverage the relations with sufficient data to assist the learning of other relations, thus achieving stable improvement in low-data scenarios. When the relation definitions are changed, our method can quickly adapt to the new ones by simply modifying the logic expressions that map time points to new event relations. The code is released at \url{https://github.com/AndrewZhe/A-Unified-Framework-for-ETRE}

Quercetin Prevents Escherichia coli O157:H7 Adhesion to Epithelial Cells via Suppressing Focal Adhesions

The attachment of Escherichia coli O157:H7 to intestinal epithelial cells is indispensable for its pathogenesis. Besides translocated-intimin receptor (Tir), E. coli O157:H7 interacts with host cell surface receptors to promote intimate adhesion. This study showed that integrin β1 was increased in Caco-2 cells upon E. coli O157:H7 infection, while Caco-2 cells subjected to integrin β1 antibody blocking or CRISPR/Cas9 knockout had reduced bacterial attachment. Infection of E. coli O157:H7 inactivated focal adhesion kinase (FAK) and paxillin, increased focal adhesion (FA) and actin polymerization, and decreased cell migration in Caco-2 cells, which were rescued by integrin β1 antibody blocking or knockout. Pre-treatment with quercetin, known for its anti-oxidant and anti-inflammatory activity, reduced bacterial infection to Caco-2 cells, which might be partially via interfering integrin β1 and FAK association augmented by E. coli O157:H7. In addition, quercetin decreased FA formation induced by bacterial infection and recovered host cell motility. Taken together, data showed that E. coli O157:H7 interacts with integrin β1 to facilitate its adhesion to host cells. Quercetin inhibits bacterial infection possibly by blocking the interaction between E. coli O157:H7 and integrin β1. Collectively, these data indicate that quercetin provides an alternative antimicrobial to mitigate and control E. coli O157:H7 intestinal infection, and suggest potential broad benefits of quercetin and related polyphenols in fighting other enteric pathogen infections