Improving Image Reconstruction for Digital Breast Tomosynthesis

Digital breast tomosynthesis (DBT) has been developed to reduce the issue of overlapping tissue in conventional 2-D mammography for breast cancer screening and diagnosis. In the DBT procedure, the patient’s breast is compressed with a paddle and a sequence of x-ray projections is taken within a small angular range. Tomographic reconstruction algorithms are then applied to these projections, generating tomosynthesized image slices of the breast, such that radiologists can read the breast slice by slice. Studies have shown that DBT can reduce both false-negative diagnoses of breast cancer and false-positive recalls compared to mammography alone. This dissertation focuses on improving image quality for DBT reconstruction. Chapter I briefly introduces the concept of DBT and the inspiration of my study. Chapter II covers the background of my research including the concept of image reconstruction, the geometry of our experimental DBT system and figures of merit for image quality. Chapter III introduces our study of the segmented separable footprint (SG) projector. By taking into account the finite size of detector element, the SG projector improves the accuracy of forward projections in iterative image reconstruction. Due to the more efficient access to memory, the SG projector is also faster than the traditional ray-tracing (RT) projector. We applied the SG projector to regular and subpixel reconstructions and demonstrated its effectiveness. Chapter IV introduces a new DBT reconstruction method with detector blur and correlated noise modeling, called the SQS-DBCN algorithm. The SQS-DBCN algorithm is able to significantly enhance microcalcifications (MC) in DBT while preserving the appearance of the soft tissue and mass margin. Comparisons between the SQS-DBCN algorithm and several modified versions of the SQS-DBCN algorithm indicate the importance of modeling different components of the system physics at the same time. Chapter V investigates truncated projection artifact (TPA) removal algorithms. Among the three algorithms we proposed, the pre-reconstruction-based projection view (PV) extrapolation method provides the best performance. Possible improvements of the other two TPA removal algorithms have been discussed. Chapter VI of this dissertation examines the effect of source blur on DBT reconstruction. Our analytical calculation demonstrates that the point spread function (PSF) of source blur is highly shift-variant. We used CatSim to simulate digital phantoms. Analysis on the reconstructed images demonstrates that a typical finite-sized focal spot (~ 0.3 mm) will not affect the image quality if the x-ray tube is stationary during the data acquisition. For DBT systems with continuous-motion data acquisition, the motion of the x-ray tube is the main cause of the effective source blur and will cause loss in the contrast of objects. Therefore modeling the source blur for these DBT systems could potentially improve the reconstructed image quality. The final chapter of this dissertation discusses a few future studies that are inspired by my PhD research.PHDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144059/1/jiabei_1.pd

Effect of source blur on digital breast tomosynthesis reconstruction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153130/1/mp13801.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153130/2/mp13801_am.pd

LBH589 Inhibits proliferation and metastasis of hepatocellular carcinoma via inhibition of gankyrin/stat3/akt pathway

Background: Gankyrin has shown to be overexpressed in human liver cancers and plays a complex role in hepatocarcinogenesis. Panobinostat (LBH589), a new hydroxamic acid-derived histone deacetylase inhibitor has shown promising anticancer effects recently. Here, we investigated the potential of LBH589 as a form of treatment for hepatocellular carcinoma (HCC). Methods: Gankyrin plasmid was transfected into HCC cells, and the cells were selected for more than 4 weeks by incubation with G418 for overexpression clones. The therapeutic effects of LBH589 were evaluated in vitro and in vivo. Cell proliferation, apoptosis, cell cycle, invasive potential, and epithelial-mesenchy-mal transition (EMT) were examined. Results: LBH589 significantly inhibited HCC growth and metastasis in vitro and in vivo. Western blotting analysis indicated that LBH589 could decrease the expression of gankyrin and subsequently reduced serine-phosphorylated Akt and tyrosine-phosphorylated STAT3 expression although the total Akt and STAT3 were unaffected. LBH589 inhibited metastasis in vitro via down-regulation of N-cadherin, vimentin, TWIST1, VEGF and up-regulation of E-cadherin. LBH589 also induced apoptosis and G1 phase arrest in HCC cell lines. Ectopic expression of gankyrin attenuated the effects of LBH589, which indicates that gankyrin might play an important role in LBH589 mediated anticancer effects. Lastly, in vivo study indicated that LBH589 inhibited tumor growth and metastasis, without discernable adverse effects comparing to control group, with abrogating gankyrin/STAT3/Akt pathway. Conclusions: Our results suggested that LBH589 could inhibit HCC growth and metastasis through down-regulating gankyrin/STAT3/Akt pathway. LBH589 may present itself as a novel therapeutic strategy for HCC

Factors associated with the incidence and the expenditure of self-medication among middle-aged and older adults in China: A cross-sectional study

BackgroundWith the accelerated ageing of population and the growing prevalence of various chronic diseases in China, self-medication plays an increasingly important role in complementing the health care system due to its convenience and economy.ObjectiveThis study aimed to investigate the incidence of self-medication and the amount of self-medication expenditure among middle-aged and older adults in China, and to explore factors associated with them.MethodsA total of 10,841 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) wave 4 which conducted in 2018 were included as the sample of this study. The two-part model was adopted to identify the association between the incidence of self-medication and the amount of self-medication expenditure and specific factors, respectively.ResultsThe incidence of self-medication among Chinese middle-aged and older adults was 62.30%, and the average total and out-of-pocket (OOP) pharmaceutical expenditure of self-medication of the self-medicated individuals were 290.50 and 264.38 Chinese yuan (CNY) respectively. Participants who took traditional Chinese medicine (TCM), self-reported fair, and poor health status, suffered from one and multiple chronic diseases had strongly higher incidence of self-medication. Older age and multiple chronic diseases were strongly associated with higher expenditure of self-medication. Those who took TCM had more self-medication expenditure, while those who drank alcohol had less.ConclusionOur study demonstrated the great prevalence of self-medication among middle-aged and older adults in China and the large pharmaceutical expenditure that come with it, especially in the high-risk groups of self-medication identified in this paper. These findings enhanced our understanding of self-medication behaviors among Chinese middle-aged and older adults and may contribute to the formulation of targeted public health policy

Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma

Background: Arsenic trioxide has been demonstrated as an effective anti-cancer drug against leukemia and solid tumors both in vitro and in vivo. However, recent phase II trials demonstrated that single agent arsenic trioxide was poorly effective against hepatocellular carcinoma (HCC), which might be due to drug resistance. Methods: Mutation detection of p53 gene in arsenic trioxide resistant HCC cell lines was performed. The therapeutic effects of arsenic trioxide and Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection, lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal transition (EMT) assays were performed to investigate the underlying mechanisms. Results: The acquisition of p53 mutation contributed to arsenic trioxide resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53) silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit the metastatic activities, while mutp53 overexpression showed the opposite effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects against arsenic trioxide resistant HCC cells, while combination of them showed significant effects. Nutlin-3 can not only increase the intracellular arsenicals through inhibition of p-gp but also promote the p73 activation and mutp53 degradation mediated by arsenic trioxide. In vivo experiments indicated that Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an orthotopic hepatic tumor model and inhibit the metastasis to lung. Conclusions: Acquisitions of p53 mutations contributed to the resistance of HCC to arsenic trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor metastasis through p73 activation and promoting mutant p53 degradation mediated by arsenic trioxide

Diphenyl Difluoroketone: A Potent Chemotherapy Candidate for Human Hepatocellular Carcinoma

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma

Regulation of Fertility by the p53 Family Members

The p53 family members, which consist of 3 transcription factors—p53, p63, and p73—are conserved during evolution. The p53 family proteins are involved in many important cellular functions, including tumor suppression (p53 and p73), the development of epithelial cell layers (p63), and the development of central nervous system and immune system (p73). Studies on p53-like proteins in low organisms have demonstrated that their primordial functions are to maintain the genomic integrity of germ cells and ensure faithful development and reproduction. In vertebrates, the p53 family proteins retain these functions in reproduction and at the same time have developed additional important functions in reproduction, such as the regulation of embryonic implantation (p53). p53 regulates embryonic implantation through transcriptional regulation of leukemia inhibitory factor (LIF). p63, in particular TAp63, is a main regulator to protect the fidelity of female germ cells during meiotic arrest. p73, in particular TAp73, regulates the ovary function and the quality of oocytes. Loss of p53, p63, or p73 genes in female mice leads to a significant decrease in fertility. These functions of the p53 family proteins in reproduction provide a plausible explanation for positive evolutionary selection observed in a group of single nucleotide polymorphisms and haplotypes in the p53 family genes. A better understanding of the functions of the p53 family proteins in reproduction may lead to new strategies for fertility treatment

Effect of source blur on digital breast tomosynthesis reconstruction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153130/1/mp13801.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153130/2/mp13801_am.pd