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Health Sciences and Technology - Ph.D. / Sc.D.

Mostrando recursos 1 - 20 de 472

  1. Computational imaging and analysis in breast cancer

    Lee, Justin Wu
    The conventional pathologic analysis of malignancies involves a qualitative characterization and integration of several factors including tumor size, general degree of differentiation, tumor heterogeneity, mitotic rate, and lymphovascular invasion. For some cancers, biomarkers such as hormone receptor expression or receptor kinase over-expression can provide additional prognostic and therapeutic guidance. Unfortunately, all of these qualitative histologic approaches, while generally accepted for directing patient care, often exhibit significant inter-observer variability resulting in inconsistent inter- and intra-institutional predictions of tumor behavior (including metastases and/or recurrence), resulting in incorrect diagnoses or treatment. Because cellular morphology is an integrated reflection of genetic and epigenetic expression,...

  2. MRI based cerebral oxygenation measures in humans : technical development for use across lifespan

    Stout, Jeffrey Neil
    MRI based cerebral oxygenation measures could enable brain-centered clinical care and improve understanding of brain energy use throughout human development. We made technical improvements to two MR oxygenation imaging techniques, and explored the concordance between various methods to quantify the cerebral metabolic rate of oxygen consumption (CMRO2 ) and other aspects of cerebral metabolism in neonates with congenital heart disease (CHD). Using a turbo gradient spin echo readout we reduced the scan time of the existing QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) technique for measurements of global oxygen extraction fraction by eightfold while improving robustness to...

  3. Selective targeting of MYC by antisense oligonucleotides

    Gill, Taylor Elizabeth
    MYC is one of the most commonly dysregulated genes across all cancers. As a master transcription factor with greater than 10,000 binding sites throughout the genome, the MYC oncoprotein coordinates a transcriptional regulatory network consisting of approximately 15% of all genes, controlling cancer hallmark expression programs responsible for cellular proliferation, growth, metabolism, and evasion from apoptosis. MYC dysregulation occurs genetically, epigenetically, and post-transcriptionally through a wide variety of mechanisms. Despite its well-characterized properties as a proto-oncogene, direct potent and selective inhibition of MYC remains a significant challenge. Models of systemic MYC inhibition utilizing inducible genetic constructs in mice have revealed...

  4. Acoustic features of impaired articulation due to amyotrophic lateral sclerosis

    Horwitz-Martin, Rachelle L. (Rachelle Laura)
    Progressive bulbar motor deterioration resulting from amyotrophic lateral sclerosis (ALS) leads to speech impairment. Despite the devastating consequences of speech impairment to life quality, few options are available to objectively assess speech motor involvement. The overarching goal of this research was to derive objective measures of speech acoustics that can be used to support clinical decision making. To achieve this goal, we obtained 121 speech samples from 33 patients with ALS who repeated the phrase "Buy Bobby a puppy" five times in succession. In total, 342 acoustic features were semi-automatically extracted from each speech recording. Pearson correlations were computed between...

  5. Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction

    Jain, Isha Himani
    Variations in atmospheric oxygen levels can be traced over evolutionary time and track closely with the development of multicellular life, speciation events, appearance of placental mammals and the creation of a cardio-respiratory system. As the final electron acceptor for aerobic ATP production, oxygen allows energy-intensive metabolic pathways to exist. Furthermore, oxygen is the most utilized substrate for known biochemical reactions, surpassing even ATP and NAD+. As a result, variations in oxygen levels have far-reaching consequences on human physiology and health. Mitochondrial disorders are the most common inborn errors of metabolism, affecting approximately 1 in 5000 live births. Patients can present...

  6. Dynamics of human decision-making : vestibular perception and neural correlates

    Lim, Koeun
    When making daily decisions, people naturally ask two questions: how soon can I make a decision, and is it a good decision? In experimental setting, humans can subjectively yet quantitatively assess choice confidence (i.e. how good) based on their perceptual precision even when a decision is made without an immediate reward or feedback. Such choice confidence has been shown to have a non-monotonic relationship with decision time (i.e. how soon), such that choice confidence can be correlated either positively or negatively with decision time depending on how decision time is constrained. However, the neural mechanisms underlying the interaction between choice...

  7. Miniaturized electromagnetic biosensors for circulating cancer biomarker detection

    Min, Changwook
    Cancer is one of leading cause of deaths, and responsible for 8.2 million deaths worldwide. Especially, 70% of deaths from cancer occur in low or mid income countries. In order to deliver affordable and accessible cancer care to low income developing countries, it is critical to develop rapid, low cost, and highly accurate tools for cancer detection and treatment. Recently, liquid biopsy and circulating cancer biomarkers such as circulating tumor cells (CTC), extracellular vesicles (EV), and cell free DNA (cfDNA) have gained great attentions for early diagnosis, prognosis, and treatment monitoring of cancer patients because they can be accessed in...

  8. An analytic model of the Cochlea and functional interpretations

    Alkhairy, Samiya Ashraf
    The cochlea is part of the peripheral auditory system that has unique and intriguing features - for example it acts as a wave-based frequency analyzer and amplifies traveling waves. The human cochlea is particularly interesting due to its critical role in our ability to process speech. To better understand how the cochlea works, we develop a model of the mammalian cochlea. We develop the model using a mixed physical-phenomenological approach. Specifically, we utilize existing work on the physics of classical box-representations of the cochlea, as well as the behavior of recent data-derived wavenumber estimates. We provide closed-form expressions for macromechanical...

  9. Quantifiable MRI changes in cerebral white matter and their importance to aging, cognition, and Alzheimer's disease

    Lindemer, Emily Rose
    Alzheimer's disease (AD) is a neurodegenerative disease for which there are no preventative or therapeutic interventions. It is currently understood to be linked to the accumulation of pathologic proteins in the brain. In the past several decades, a strong body of evidence has accumulated that is suggestive of a vascular-related pathway in AD. A deeper understanding of this phenomenon is critical in advancing our understanding of the AD biological process as well and may lead to the discovery of novel therapeutic targets. A common age-related change in the brain is the development of white matter signal abnormalities (WMSA) as seen...

  10. Quantifiable MRI changes in cerebral white matter and their importance to aging, cognition, and Alzheimer's disease

    Lindemer, Emily Rose
    Alzheimer's disease (AD) is a neurodegenerative disease for which there are no preventative or therapeutic interventions. It is currently understood to be linked to the accumulation of pathologic proteins in the brain. In the past several decades, a strong body of evidence has accumulated that is suggestive of a vascular-related pathway in AD. A deeper understanding of this phenomenon is critical in advancing our understanding of the AD biological process as well and may lead to the discovery of novel therapeutic targets. A common age-related change in the brain is the development of white matter signal abnormalities (WMSA) as seen...

  11. Drug eluting prosthetic joints through drug cluster morphology control

    Suhardi, Vincentius Jeremy
    More than one million joint replacements are performed in the USA annually. However, around 10 % of patients require revision surgery within 10 years with prosthetic joint infections (PJI) as a common reason. PJI has a recurrence rate of 16 %, a mortality rate of 2.5 %, and end-stage treatments involving arthrodesis and amputation. Most drug eluting polymers that were in development to address this problem failed due to toxic degradation products, insufficient drug release, and insufficient mechanical strength. The gold standard of treatment uses antibiotic eluting bone cement which has a mechanical failure rate of 26-60 % within 49-54...

  12. Drug eluting prosthetic joints through drug cluster morphology control

    Suhardi, Vincentius Jeremy
    More than one million joint replacements are performed in the USA annually. However, around 10 % of patients require revision surgery within 10 years with prosthetic joint infections (PJI) as a common reason. PJI has a recurrence rate of 16 %, a mortality rate of 2.5 %, and end-stage treatments involving arthrodesis and amputation. Most drug eluting polymers that were in development to address this problem failed due to toxic degradation products, insufficient drug release, and insufficient mechanical strength. The gold standard of treatment uses antibiotic eluting bone cement which has a mechanical failure rate of 26-60 % within 49-54...

  13. Compact tomographic X-ray phase-contrast imaging of breast cancer

    Xu, Ling, Ph. D. Massachusetts Institute of Technology
    Non-invasive imaging plays an important role throughout the clinical diagnosis and management process of breast cancer. Unfortunately, existing imaging methods lack the combination of spatial resolution and soft-tissue contrast necessary to visualize pathological changes in the breast. X-ray phase-contrast imaging (XPCI) has emerged as a promising modality for providing enhanced soft tissue differentiation due to its inherent source of contrast being derived from diffraction effects rather than absorption. Studies using synchrotron sources have demonstrated the potential of XPCI in revealing structural details of the breast undetectable via existing modalities. However, the reliance on high-brilliance synchrotron sources significantly limits the use...

  14. Compact tomographic X-ray phase-contrast imaging of breast cancer

    Xu, Ling, Ph. D. Massachusetts Institute of Technology
    Non-invasive imaging plays an important role throughout the clinical diagnosis and management process of breast cancer. Unfortunately, existing imaging methods lack the combination of spatial resolution and soft-tissue contrast necessary to visualize pathological changes in the breast. X-ray phase-contrast imaging (XPCI) has emerged as a promising modality for providing enhanced soft tissue differentiation due to its inherent source of contrast being derived from diffraction effects rather than absorption. Studies using synchrotron sources have demonstrated the potential of XPCI in revealing structural details of the breast undetectable via existing modalities. However, the reliance on high-brilliance synchrotron sources significantly limits the use...

  15. MR-assisted PET data optimization for simultaneous dual-modality imaging in dementia

    Chen, Kevin Tze-Hsiang
    Recent advances have allowed the hardware integration of positron emission tomography (PET) and magnetic resonance imaging (MRI). The spatiotemporally correlated data acquisition opened up opportunities for numerous applications. Furthermore, the MRI data can be utilized to improve the PET scanner performance. While PET has many advantages, including the fact that it could provide a quantitative means to assess in vivo biological processes, its accuracy is confounded by several factors. For example, attenuation correction is required to account for the interactions of the annihilation photons in the subject; motion correction is needed to minimize image degradation due to subject movements; partial...

  16. MR-assisted PET data optimization for simultaneous dual-modality imaging in dementia

    Chen, Kevin Tze-Hsiang
    Recent advances have allowed the hardware integration of positron emission tomography (PET) and magnetic resonance imaging (MRI). The spatiotemporally correlated data acquisition opened up opportunities for numerous applications. Furthermore, the MRI data can be utilized to improve the PET scanner performance. While PET has many advantages, including the fact that it could provide a quantitative means to assess in vivo biological processes, its accuracy is confounded by several factors. For example, attenuation correction is required to account for the interactions of the annihilation photons in the subject; motion correction is needed to minimize image degradation due to subject movements; partial...

  17. Decipher in situ signaling and complex genetics with cellular recording and combinatorial perturbations

    Cui, Cheryl H. (Cheryl Hao)
    The complex, dynamic, and responsive behavior of cells arises from integrated signaling pathways and regulatory networks. With advancement in our ability to engineer mammalian cells, we harness a novel set of molecular tools to develop synthetic biology-enabled applications that help facilitate our understanding of complex biological networks and cellular behaviors. The recent discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated (Cas) system from prokaryotic adaptive immune system demonstrated unprecedented genome editing efficiency and programmability in sequence specific genome editing of mammalian cells. In this thesis, I utilized the CRISPR-Cas system to construct a combinatorial genetic perturbation platform that...

  18. The role of the PD-1 pathway in the tumor microenvironment

    Juneja, Vikram R
    The immune system has proven valuable in the fight against cancer. Therapies that unleash a T cell response against tumors have led to durable remissions in multiple cancers. Specifically, antibodies blocking the programmed death (PD)-1 pathway have been approved for the treatment of metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma, amongst others. However, only a limited number of patients respond to these therapies. The field is now trying to determine combination strategies and biomarkers to extend the benefits of these therapies to additional patients in a rationale manner. A fundamental challenge towards this goal is that the...

  19. Biological and medical implications of discordance in CpG methylation

    Clement, Mark Kendell
    DNA methylation is an important epigenetic mark that is linked to the regulation of gene expression. It is a critical part of controlling cellular identity and is essential for normal development. DNA methylation is generally studied by comparing methylation levels at individual cytosines or computing region-level averages to identify differential methylation. Here we extended this classic viewpoint by capitalizing on a unique feature of next-generation sequencing, which provides the methylation status of CpGs that are located on the same sequencing read and hence originate from the same DNA molecule. When comparing methylation states of CpGs on the same read, we...

  20. Skeletal adaptation to reduced mechanical loading

    Ellman, Rachel
    Bone adapts its mass and architecture in response to its mechanical environment. Yet control of this process by mechanical cues is poorly understood, particularly for unloading. Defining the fundamental mechano-regulation of bone adaptation is critical for the better understanding and mitigation of bone loss in astronauts as well as clinical conditions such as spinal cord injury, stroke, muscular dystrophy, and bed rest. The overall goal of this work was to study skeletal adaptation to varying amounts of reduced loading to help delineate the relationship between mechanical stimuli and skeletal adaptation. We first examined the relative contribution of muscle and gravitational...

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