Matching Items (5)
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- All Subjects: Medical Imaging
- All Subjects: Fluorescent
- Creators: Liang, Jianming
- Creators: Guo, Jia
Description
The understanding of normal human physiology and disease pathogenesis shows great promise for progress with increasing ability to profile genomic loci and transcripts in single cells in situ. Using biorthogonal cleavable fluorescent oligonucleotides, a highly multiplexed single-cell in situ RNA and DNA analysis is reported. In this report, azide-based cleavable linker connects oligonucleotides to fluorophores to show nucleic acids through in situ hybridization. Post-imaging, the fluorophores are effectively cleaved off in half an hour without loss of RNA or DNA integrity. Through multiple cycles of hybridization, imaging, and cleavage this approach proves to quantify thousands of different RNA species or genomic loci because of single-molecule sensitivity in single cells in situ. Different nucleic acids can be imaged by shown by multi-color staining in each hybridization cycle, and that multiple hybridization cycles can be run on the same specimen. It is shown that in situ analysis of DNA, RNA and protein can be accomplished using both cleavable fluorescent antibodies and oligonucleotides. The highly multiplexed imaging platforms will have the potential for wide applications in both systems biology and biomedical research. Thus, proving to be cost effective and time effective.
ContributorsSamuel, Adam David (Author) / Guo, Jia (Thesis director) / Liu, Wei (Committee member) / Wang, Xu (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The ability to profile proteins allows us to gain a deeper understanding of organization, regulation, and function of different biological systems. Many technologies are currently being used in order to accurately perform the protein profiling. Some of these technologies include mass spectrometry, microarray based analysis, and fluorescence microscopy. Deeper analysis of these technologies have demonstrated limitations which have taken away from either the efficiency or the accuracy of the results. The objective of this project was to develop a technology in which highly multiplexed single cell in situ protein analysis can be completed in a comprehensive manner without the loss of the protein targets. This was accomplished in the span of 3 steps which is referred to as the immunofluorescence cycle. Antibodies with attached fluorophores with the help of novel azide-based cleavable linker are used to detect protein targets. Fluorescence imaging and data storage procedures are done on the targets and then the fluorophores are cleaved from the antibodies without the loss of the protein targets. Continuous cycles of the immunofluorescence procedure can help create a comprehensive and quantitative profile of the protein. The development of such a technique will not only help us understand biological systems such as solid tumor, brain tissues, and developing embryos. But it will also play a role in real-world applications such as signaling network analysis, molecular diagnosis and cellular targeted therapies.
ContributorsGupta, Aakriti (Author) / Guo, Jia (Thesis director) / Liang, Jianming (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Alzheimer’s disease (AD), is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. There is growing interest in identifying brain image biomarkers that help evaluate AD risk pre-symptomatically. High-dimensional non-linear pattern classification methods have been applied to structural magnetic resonance images (MRI’s) and used to discriminate between clinical groups in Alzheimers progression. Using Fluorodeoxyglucose (FDG) positron emission tomography (PET) as the pre- ferred imaging modality, this thesis develops two independent machine learning based patch analysis methods and uses them to perform six binary classification experiments across different (AD) diagnostic categories. Specifically, features were extracted and learned using dimensionality reduction and dictionary learning & sparse coding by taking overlapping patches in and around the cerebral cortex and using them as fea- tures. Using AdaBoost as the preferred choice of classifier both methods try to utilize 18F-FDG PET as a biological marker in the early diagnosis of Alzheimer’s . Addi- tional we investigate the involvement of rich demographic features (ApoeE3, ApoeE4 and Functional Activities Questionnaires (FAQ)) in classification. The experimental results on Alzheimer’s Disease Neuroimaging initiative (ADNI) dataset demonstrate the effectiveness of both the proposed systems. The use of 18F-FDG PET may offer a new sensitive biomarker and enrich the brain imaging analysis toolset for studying the diagnosis and prognosis of AD.
ContributorsSrivastava, Anant (Author) / Wang, Yalin (Thesis advisor) / Bansal, Ajay (Thesis advisor) / Liang, Jianming (Committee member) / Arizona State University (Publisher)
Created2017
Description
Alzheimer’s Disease (AD), a neurodegenerative disease is a progressive disease that affects the brain gradually with time and worsens. Reliable and early diagnosis of AD and its prodromal stages (i.e. Mild Cognitive Impairment(MCI)) is essential. Fluorodeoxyglucose (FDG) positron emission tomography (PET) measures the decline in the regional cerebral metabolic rate for glucose, offering a reliable metabolic biomarker even on presymptomatic AD patients. PET scans provide functional information that is unique and unavailable using other types of imaging. The computational efficacy of FDG-PET data alone, for the classification of various Alzheimer’s Diagnostic categories (AD, MCI (LMCI, EMCI), Control) has not been studied. This serves as motivation to correctly classify the various diagnostic categories using FDG-PET data. Deep learning has recently been applied to the analysis of structural and functional brain imaging data. This thesis is an introduction to a deep learning based classification technique using neural networks with dimensionality reduction techniques to classify the different stages of AD based on FDG-PET image analysis.
This thesis develops a classification method to investigate the performance of FDG-PET as an effective biomarker for Alzheimer's clinical group classification. This involves dimensionality reduction using Probabilistic Principal Component Analysis on max-pooled data and mean-pooled data, followed by a Multilayer Feed Forward Neural Network which performs binary classification. Max pooled features result into better classification performance compared to results on mean pooled features. Additionally, experiments are done to investigate if the addition of important demographic features such as Functional Activities Questionnaire(FAQ), gene information helps improve performance. Classification results indicate that our designed classifiers achieve competitive results, and better with the additional of demographic features.
This thesis develops a classification method to investigate the performance of FDG-PET as an effective biomarker for Alzheimer's clinical group classification. This involves dimensionality reduction using Probabilistic Principal Component Analysis on max-pooled data and mean-pooled data, followed by a Multilayer Feed Forward Neural Network which performs binary classification. Max pooled features result into better classification performance compared to results on mean pooled features. Additionally, experiments are done to investigate if the addition of important demographic features such as Functional Activities Questionnaire(FAQ), gene information helps improve performance. Classification results indicate that our designed classifiers achieve competitive results, and better with the additional of demographic features.
ContributorsSingh, Shibani (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Arizona State University (Publisher)
Created2017
Description
There is intense interest in adopting computer-aided diagnosis (CAD) systems, particularly those developed based on deep learning algorithms, for applications in a number of medical specialties. However, success of these CAD systems relies heavily on large annotated datasets; otherwise, deep learning often results in algorithms that perform poorly and lack generalizability. Therefore, this dissertation seeks to address this critical problem: How to develop efficient and effective deep learning algorithms for medical applications where large annotated datasets are unavailable. In doing so, we have outlined three specific aims: (1) acquiring necessary annotations efficiently from human experts; (2) utilizing existing annotations effectively from advanced architecture; and (3) extracting generic knowledge directly from unannotated images. Our extensive experiments indicate that, with a small part of the dataset annotated, the developed deep learning methods can match, or even outperform those that require annotating the entire dataset. The last part of this dissertation presents the importance and application of imaging in healthcare, elaborating on how the developed techniques can impact several key facets of the CAD system for detecting pulmonary embolism. Further research is necessary to determine the feasibility of applying these advanced deep learning technologies in clinical practice, particularly when annotation is limited. Progress in this area has the potential to enable deep learning algorithms to generalize to real clinical data and eventually allow CAD systems to be employed in clinical medicine at the point of care.
ContributorsZhou, Zongwei (Author) / Liang, Jianming (Thesis advisor) / Shortliffe, Edward H (Committee member) / Greenes, Robert A (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2021