Matching Items (12)

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Evaluating and controlling glioblastoma infiltration

Description

Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months.

Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months. Increasing the extent of GBM resection increases patient survival. However, extending neurosurgical margins also threatens the removal of eloquent brain. For this reason, the infiltrative nature of GBM is an obstacle to its complete resection. We hypothesize that targeting genes and proteins that regulate GBM motility, and developing techniques that safely enhance extent of surgical resection, will improve GBM patient survival by decreasing infiltration into eloquent brain regions and enhancing tumor cytoreduction during surgery. Chapter 2 of this dissertation describes a gene and protein we identified; aquaporin-1 (aqp1) that enhances infiltration of GBM. In chapter 3, we describe a method for enhancing the diagnostic yield of GBM patient biopsies which will assist in identifying future molecular targets for GBM therapies. In chapter 4 we develop an intraoperative optical imaging technique that will assist identifying GBM and its infiltrative margins during surgical resection. The topic of this dissertation aims to target glioblastoma infiltration from molecular and cellular biology and neurosurgical disciplines. In the introduction we; 1. Provide a background of GBM and current therapies. 2. Discuss a protein we found that decreases GBM survival. 3. Describe an imaging modality we utilized for improving the quality of accrued patient GBM samples. 4. We provide an overview of intraoperative contrast agents available for neurosurgical resection of GBM, and discuss a new agent we studied for intraoperative visualization of GBM.

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  • 2014

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Multi-parametric MRI Study of Brain Insults (Traumatic Brain Injury and Brain Tumor) in Animal Models

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The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate

The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate projects make up the basis of this thesis. The first part focuses on obtaining prognostic information at early stages in the case of Traumatic Brain Injury (TBI) in rat animal model using imaging data acquired at 24-hours and 7-days post injury. The obtained parametric T2 and diffusion values from DTI (Diffusion Tensor Imaging) showed significant deviations in the signal intensities from the control and were potentially useful as an early indicator of the severity of post-traumatic injury damage. DTI was especially critical in distinguishing between the cytotoxic and vasogenic edema and in identification of injury regions resolving to normal control values by day-7. These results indicate the potential of quantitative MRI as a clinical marker in predicting prognosis following TBI. The second part of this thesis focuses on studying the effect of novel therapeutic strategies employing dendritic cell (DC) based vaccinations in mice glioma model. The treatment cohorts included comparing a single dose of Azacytidine drug vs. mice getting three doses of drug per week. Another cohort was used as an untreated control group. The MRI results did not show any significant changes in between the two treated cohorts with no reduction in tumor volumes compared to the control group. The future studies would be focused on issues regarding the optimal dose for the application of DC vaccine. Together, the quantitative MRI plays an important role in the prognosis and diagnosis of the above mentioned pathologies, providing essential information about the anatomical location, micro-structural tissue environment, lesion volume and treatment response.

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  • 2014

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Flexible electronics and display technology for medical, biological, and life science applications

Description

This work explores how flexible electronics and display technology can be applied to develop new biomedical devices for medical, biological, and life science applications. It demonstrates how new biomedical devices

This work explores how flexible electronics and display technology can be applied to develop new biomedical devices for medical, biological, and life science applications. It demonstrates how new biomedical devices can be manufactured by only modifying or personalizing the upper layers of a conventional thin film transistor (TFT) display process. This personalization was applied first to develop and demonstrate the world's largest flexible digital x-ray detector for medical and industrial imaging, and the world's first flexible ISFET pH biosensor using TFT technology. These new, flexible, digital x-ray detectors are more durable than conventional glass substrate x-ray detectors, and also can conform to the surface of the object being imaged. The new flexible ISFET pH biosensors are >10X less expensive to manufacture than comparable CMOS-based ISFETs and provide a sensing area that is orders of magnitude larger than CMOS-based ISFETs. This allows for easier integration with area intensive chemical and biological recognition material as well as allow for a larger number of unique recognition sites for low cost multiple disease and pathogen detection.

The flexible x-ray detector technology was then extended to demonstrate the viability of a new technique to seamlessly combine multiple smaller flexible x-ray detectors into a single very large, ultimately human sized, composite x-ray detector for new medical imaging applications such as single-exposure, low-dose, full-body digital radiography. Also explored, is a new approach to increase the sensitivity of digital x-ray detectors by selectively disabling rows in the active matrix array that are not part of the imaged region. It was then shown how high-resolution, flexible, organic light-emitting diode display (OLED) technology can be used to selectively stimulate and/or silence small groups of neurons on the cortical surface or within the deep brain as a potential new tool to diagnose and treat, as well as understand, neurological diseases and conditions. This work also explored the viability of a new miniaturized high sensitivity fluorescence measurement-based lab-on-a-chip optical biosensor using OLED display and a-Si:H PiN photodiode active matrix array technology for point-of-care diagnosis of multiple disease or pathogen biomarkers in a low cost disposable configuration.

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  • 2014

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Small blob detection in medical images

Description

Recent advances in medical imaging technology have greatly enhanced imaging based diagnosis which requires computational effective and accurate algorithms to process the images (e.g., measure the objects) for quantitative assessment.

Recent advances in medical imaging technology have greatly enhanced imaging based diagnosis which requires computational effective and accurate algorithms to process the images (e.g., measure the objects) for quantitative assessment. In this dissertation, one type of imaging objects is of interest: small blobs. Example small blob objects are cells in histopathology images, small breast lesions in ultrasound images, glomeruli in kidney MR images etc. This problem is particularly challenging because the small blobs often have inhomogeneous intensity distribution and indistinct boundary against the background.

This research develops a generalized four-phased system for small blob detections. The system includes (1) raw image transformation, (2) Hessian pre-segmentation, (3) feature extraction and (4) unsupervised clustering for post-pruning. First, detecting blobs from 2D images is studied where a Hessian-based Laplacian of Gaussian (HLoG) detector is proposed. Using the scale space theory as foundation, the image is smoothed via LoG. Hessian analysis is then launched to identify the single optimal scale based on which a pre-segmentation is conducted. Novel Regional features are extracted from pre-segmented blob candidates and fed to Variational Bayesian Gaussian Mixture Models (VBGMM) for post pruning. Sixteen cell histology images and two hundred cell fluorescent images are tested to demonstrate the performances of HLoG. Next, as an extension, Hessian-based Difference of Gaussians (HDoG) is proposed which is capable to identify the small blobs from 3D images. Specifically, kidney glomeruli segmentation from 3D MRI (6 rats, 3 humans) is investigated. The experimental results show that HDoG has the potential to automatically detect glomeruli, enabling new measurements of renal microstructures and pathology in preclinical and clinical studies. Realizing the computation time is a key factor impacting the clinical adoption, the last phase of this research is to investigate the data reduction technique for VBGMM in HDoG to handle large-scale datasets. A new coreset algorithm is developed for variational Bayesian mixture models. Using the same MRI dataset, it is observed that the four-phased system with coreset-VBGMM has similar performance as using the full dataset but about 20 times faster.

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  • 2015

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Rapid 3D phase contrast magnetic resonance angiography through high-moment velocity encoding and 3D parallel imaging

Description

Phase contrast magnetic resonance angiography (PCMRA) is a non-invasive imaging modality that is capable of producing quantitative vascular flow velocity information. The encoding of velocity information can significantly increase the

Phase contrast magnetic resonance angiography (PCMRA) is a non-invasive imaging modality that is capable of producing quantitative vascular flow velocity information. The encoding of velocity information can significantly increase the imaging acquisition and reconstruction durations associated with this technique. The purpose of this work is to provide mechanisms for reducing the scan time of a 3D phase contrast exam, so that hemodynamic velocity data may be acquired robustly and with a high sensitivity. The methods developed in this work focus on the reduction of scan duration and reconstruction computation of a neurovascular PCMRA exam. The reductions in scan duration are made through a combination of advances in imaging and velocity encoding methods. The imaging improvements are explored using rapid 3D imaging techniques such as spiral projection imaging (SPI), Fermat looped orthogonally encoded trajectories (FLORET), stack of spirals and stack of cones trajectories. Scan durations are also shortened through the use and development of a novel parallel imaging technique called Pretty Easy Parallel Imaging (PEPI). Improvements in the computational efficiency of PEPI and in general MRI reconstruction are made in the area of sample density estimation and correction of 3D trajectories. A new method of velocity encoding is demonstrated to provide more efficient signal to noise ratio (SNR) gains than current state of the art methods. The proposed velocity encoding achieves improved SNR through the use of high gradient moments and by resolving phase aliasing through the use measurement geometry and non-linear constraints.

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  • 2011

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Ensuring high-quality colonoscopy by reducing polyp miss-rates

Description

Colorectal cancer is the second-highest cause of cancer-related deaths in the United States with approximately 50,000 estimated deaths in 2015. The advanced stages of colorectal cancer has a poor five-year

Colorectal cancer is the second-highest cause of cancer-related deaths in the United States with approximately 50,000 estimated deaths in 2015. The advanced stages of colorectal cancer has a poor five-year survival rate of 10%, whereas the diagnosis in early stages of development has showed a more favorable five-year survival rate of 90%. Early diagnosis of colorectal cancer is achievable if colorectal polyps, a possible precursor to cancer, are detected and removed before developing into malignancy.

The preferred method for polyp detection and removal is optical colonoscopy. A colonoscopic procedure consists of two phases: (1) insertion phase during which a flexible endoscope (a flexible tube with a tiny video camera at the tip) is advanced via the anus and then gradually to the end of the colon--called the cecum, and (2) withdrawal phase during which the endoscope is gradually withdrawn while colonoscopists examine the colon wall to find and remove polyps. Colonoscopy is an effective procedure and has led to a significant decline in the incidence and mortality of colon cancer. However, despite many screening and therapeutic advantages, 1 out of every 4 polyps and 1 out of 13 colon cancers are missed during colonoscopy.

There are many factors that contribute to missed polyps and cancers including poor colon preparation, inadequate navigational skills, and fatigue. Poor colon preparation results in a substantial portion of colon covered with fecal content, hindering a careful examination of the colon. Inadequate navigational skills can prevent a colonoscopist from examining hard-to-reach regions of the colon that may contain a polyp. Fatigue can manifest itself in the performance of a colonoscopist by decreasing diligence and vigilance during procedures. Lack of vigilance may prevent a colonoscopist from detecting the polyps that briefly appear in the colonoscopy videos. Lack of diligence may result in hasty examination of the colon that is likely to miss polyps and lesions.

To reduce polyp and cancer miss rates, this research presents a quality assurance system with 3 components. The first component is an automatic polyp detection system that highlights the regions with suspected polyps in colonoscopy videos. The goal is to encourage more vigilance during procedures. The suggested polyp detection system consists of several novel modules: (1) a new patch descriptor that characterizes image appearance around boundaries more accurately and more efficiently than widely-used patch descriptors such HoG, LBP, and Daisy; (2) A 2-stage classification framework that is able to enhance low level image features prior to classification. Unlike the traditional way of image classification where a single patch undergoes the processing pipeline, our system fuses the information extracted from a pair of patches for more accurate edge classification; (3) a new vote accumulation scheme that robustly localizes objects with curvy boundaries in fragmented edge maps. Our voting scheme produces a probabilistic output for each polyp candidate but unlike the existing methods (e.g., Hough transform) does not require any predefined parametric model of the object of interest; (4) and a unique three-way image representation coupled with convolutional neural networks (CNNs) for classifying the polyp candidates. Our image representation efficiently captures a variety of features such as color, texture, shape, and temporal information and significantly improves the performance of the subsequent CNNs for candidate classification. This contrasts with the exiting methods that mainly rely on a subset of the above image features for polyp detection. Furthermore, this research is the first to investigate the use of CNNs for polyp detection in colonoscopy videos.

The second component of our quality assurance system is an automatic image quality assessment for colonoscopy. The goal is to encourage more diligence during procedures by warning against hasty and low quality colon examination. We detect a low quality colon examination by identifying a number of consecutive non-informative frames in videos. We base our methodology for detecting non-informative frames on two key observations: (1) non-informative frames

most often show an unrecognizable scene with few details and blurry edges and thus their information can be locally compressed in a few Discrete Cosine Transform (DCT) coefficients; however, informative images include much more details and their information content cannot be summarized by a small subset of DCT coefficients; (2) information content is spread all over the image in the case of informative frames, whereas in non-informative frames, depending on image artifacts and degradation factors, details may appear in only a few regions. We use the former observation in designing our global features and the latter in designing our local image features. We demonstrated that the suggested new features are superior to the existing features based on wavelet and Fourier transforms.

The third component of our quality assurance system is a 3D visualization system. The goal is to provide colonoscopists with feedback about the regions of the colon that have remained unexamined during colonoscopy, thereby helping them improve their navigational skills. The suggested system is based on a new 3D reconstruction algorithm that combines depth and position information for 3D reconstruction. We propose to use a depth camera and a tracking sensor to obtain depth and position information. Our system contrasts with the existing works where the depth and position information are unreliably estimated from the colonoscopy frames. We conducted a use case experiment, demonstrating that the suggested 3D visualization system can determine the unseen regions of the navigated environment. However, due to technology limitations, we were not able to evaluate our 3D visualization system using a phantom model of the colon.

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  • 2015

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Fast, variable system delay correction for spiral MRI

Description

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.

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  • 2013

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Coronary artery plaque assessment with fast switched dual energy X-ray computed tomography angiography

Description

Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide

Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques.

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  • 2013

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Magnetic resonance imaging of the brain: enabling advances in efficient non-cartesian sampling

Description

Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to

Magnetic Resonance Imaging (MRI) is limited in speed and resolution by the inherently low Signal to Noise Ratio (SNR) of the underlying signal. Advances in sampling efficiency are required to support future improvements in scan time and resolution. SNR efficiency is improved by sampling data for a larger proportion of total imaging time. This is challenging as these acquisitions are typically subject to artifacts such as blurring and distortions. The current work proposes a set of tools to help with the creation of different types of SNR efficient scans. An SNR efficient pulse sequence providing diffusion imaging data with full brain coverage and minimal distortion is first introduced. The proposed method acquires single-shot, low resolution image slabs which are then combined to reconstruct the full volume. An iterative deblurring algorithm allowing the lengthening of spiral SPoiled GRadient echo (SPGR) acquisition windows in the presence of rapidly varying off-resonance fields is then presented. Finally, an efficient and practical way of collecting 3D reformatted data is proposed. This method constitutes a good tradeoff between 2D and 3D neuroimaging in terms of scan time and data presentation. These schemes increased the SNR efficiency of currently existing methods and constitute key enablers for the development of SNR efficient MRI.

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  • 2011

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In support of high quality 3-D ultrasound imaging for hand-held devices

Description

Three dimensional (3-D) ultrasound is safe, inexpensive, and has been shown to drastically improve system ease-of-use, diagnostic efficiency, and patient throughput. However, its high computational complexity and resulting high power

Three dimensional (3-D) ultrasound is safe, inexpensive, and has been shown to drastically improve system ease-of-use, diagnostic efficiency, and patient throughput. However, its high computational complexity and resulting high power consumption has precluded its use in hand-held applications.

In this dissertation, algorithm-architecture co-design techniques that aim to make hand-held 3-D ultrasound a reality are presented. First, image enhancement methods to improve signal-to-noise ratio (SNR) are proposed. These include virtual source firing techniques and a low overhead digital front-end architecture using orthogonal chirps and orthogonal Golay codes.

Second, algorithm-architecture co-design techniques to reduce the power consumption of 3-D SAU imaging systems is presented. These include (i) a subaperture multiplexing strategy and the corresponding apodization method to alleviate the signal bandwidth bottleneck, and (ii) a highly efficient iterative delay calculation method to eliminate complex operations such as multiplications, divisions and square-root in delay calculation during beamforming. These techniques were used to define Sonic Millip3De, a 3-D die stacked architecture for digital beamforming in SAU systems. Sonic Millip3De produces 3-D high resolution images at 2 frames per second with system power consumption of 15W in 45nm technology.

Third, a new beamforming method based on separable delay decomposition is proposed to reduce the computational complexity of the beamforming unit in an SAU system. The method is based on minimizing the root-mean-square error (RMSE) due to delay decomposition. It reduces the beamforming complexity of a SAU system by 19x while providing high image fidelity that is comparable to non-separable beamforming. The resulting modified Sonic Millip3De architecture supports a frame rate of 32 volumes per second while maintaining power consumption of 15W in 45nm technology.

Next a 3-D plane-wave imaging system that utilizes both separable beamforming and coherent compounding is presented. The resulting system has computational complexity comparable to that of a non-separable non-compounding baseline system while significantly improving contrast-to-noise ratio and SNR. The modified Sonic Millip3De architecture is now capable of generating high resolution images at 1000 volumes per second with 9-fire-angle compounding.

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  • 2015