Patient-specific anatomical illustration via model-guided texture synthesis

Medical illustrations can make powerful use of textures to attractively, effectively, and efficiently visualize the appearance of the surface or cut surface of anatomic structures. It can do this by implying the anatomic structure's physical composition and clarifying its identity and 3-D shape. Current visualization methods are only capable of conveying detailed information about the orientation, internal structure, and other local properties of the anatomical objects for a typical individual, not for a particular patient. Although one can derive the shape of the individual patient's object from CT or MRI, it is important to apply these illustrative techniques to those particular shapes. In this research patient-specific anatomical illustrations are created by model-guided texture synthesis (MGTS). Given 2D exemplar textures and model-based guidance information as input, MGTS uses exemplar-based texture synthesis techniques to create patient-specific surface and solid textures. It consists of three main components. The first component includes a novel texture metamorphosis approach for creating interpolated exemplar textures given two exemplar textures. This component uses an energy optimization scheme derived from optimal control principles that utilizes intensity and structure information in obtaining the transformation. The second component consists of creating the model-based guidance information, such as directions and layers, for that specific model. This component uses coordinates implied by discrete medial 3D anatomical models (m-reps). The last component accomplishes exemplar-based texture synthesis by textures whose characteristics are spatially variant on and inside the 3D models. It considers the exemplar textures from the first component and guidance information from the second component in synthesizing high-quality, high-resolution solid and surface textures. Patient-specific illustrations with a variety of textures for different anatomical models, such as muscles and bones, are shown to be useful for our clinician to comprehend the shape of the models under radiation dose and to distinguish the models from one another

Baroque Pianism: Perspectives on Playing Baroque Keyboard Music on the Piano, with Emphasis on Bach’s Fugues in the \u3ci\u3eWell-Tempered Clavier\u3c/i\u3e

In a famous quote, Schumann described the fugues in Bach\u27s Well-tempered Clavier as pianists’ “daily bread.” This dissertation explains how these fugues can be pianists’ practical daily bread by encouraging them to explore a virtuosity of subtlety. I assert that the compositional complexity in these fugues increases pianistic challenges in both interpretive and technical aspects; these challenges can lead pianists to explore a multi-faced pianistic awareness in a way that they may not encounter when performing other styles of music

Visual analytics methods for shape analysis of biomedical images exemplified on rodent skull morphology

In morphometrics and its application fields like medicine and biology experts are interested in causal relations of variation in organismic shape to phylogenetic, ecological, geographical, epidemiological or disease factors - or put more succinctly by Fred L. Bookstein, morphometrics is "the study of covariances of biological form". In order to reveal causes for shape variability, targeted statistical analysis correlating shape features against external and internal factors is necessary but due to the complexity of the problem often not feasible in an automated way. Therefore, a visual analytics approach is proposed in this thesis that couples interactive visualizations with automated statistical analyses in order to stimulate generation and qualitative assessment of hypotheses on relevant shape features and their potentially affecting factors. To this end long established morphometric techniques are combined with recent shape modeling approaches from geometry processing and medical imaging, leading to novel visual analytics methods for shape analysis. When used in concert these methods facilitate targeted analysis of characteristic shape differences between groups, co-variation between different structures on the same anatomy and correlation of shape to extrinsic attributes. Here a special focus is put on accurate modeling and interactive rendering of image deformations at high spatial resolution, because that allows for faithful representation and communication of diminutive shape features, large shape differences and volumetric structures. The utility of the presented methods is demonstrated in case studies conducted together with a collaborating morphometrics expert. As exemplary model structure serves the rodent skull and its mandible that are assessed via computed tomography scans

Essential techniques for improving visual realism of laparoscopic surgery simulation.

With the prevalence of laparoscopic surgery, the request for reliable training and assessment is becoming increasingly important. The traditional way of training is both time consuming and cost intensive, and may cause ethical or moral issues. With the development of computer technologies, virtual reality has entered the world of consumer electronics as a new way to enhance tactile and visual sensory experiences. Virtual reality based surgical skill training gradually becomes an effective supplementary to the traditional laparoscopic skill training in many surgical theatres. To provide high fidelity virtual surgery training experiences, the presentation of the virtual world should have the same level of realism as what surgeons see and feel during real operations. However, the weak computing power limits the potential level of details on the graphics presentation and physical behaviour of virtual objects, which will further influence the fidelity of tactile interaction. Achieving visual realism (realistic graphics presentation and accurate physical behaviour) and good user experience using limited computing resources is the main challenge for laparoscopic surgery simulation. The topic of visual realism in laparoscopic surgery simulation has not been well researched. This topic mainly relates to the area of 3D anatomy modeling, soft body simulation and rendering. Current researches in computer graphics and game communities are not tailored for laparoscopic surgery simulation. The direct use of those techniques in developing surgery simulators will often result in poor quality anatomy model, inaccurate simulation, low fidelity visual effect, poor user experience and inefficient production pipeline, which significantly influence the visual realism of the virtual world. The development of laparoscopic surgery simulator is an interdiscipline of computer graphics, computational physics and haptics. However, current researches barely focus on the study of tailored techniques and efficient production pipeline which often result in the long term research cycle and daunting cost for simulator development. This research is aiming at improving the visual realism of laparoscopic surgery simulation from the perspective of computer graphics. In this research, a set of tailor techniques have been proposed to improve the visual realism for laparoscopic surgery simulation. For anatomy modeling, an automatic and efficient 3D anatomy conversion pipeline is proposed which can convert bad quality 3D anatomy into simulation ready state while preserving the original model’s surface parameterization property. For simulation, a soft tissue simulation pipeline is pro- posed which can provide multi-layer heterogeneous soft tissue modeling and intuitive physically editable simulation based on uniform polynomial based hyperelastic material representation. For interaction, a collision detection and interaction system based on adaptive circumphere structure is proposed which supports robust and efficient sliding con- tact, energized dissection and clip. For rendering, a multi-layer soft tissue rendering pipeline is proposed which decomposed the multi-layer structure of soft tissue into corresponding material asset required by state-of-art rendering techniques. Based on this research, a system framework for building a laparoscopic surgery simulator is also proposed to test the feasibility of those tailored techniques

INTEGRATION OF BIOMEDICAL IMAGING AND TRANSLATIONAL APPROACHES FOR MANAGEMENT OF HEAD AND NECK CANCER

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We used anatomical MRIs for the RT dose adaptation purpose. Our findings showed that after proper standardization of the immobilization and image acquisition techniques, we can achieve high geometric accuracy. These images can then be used to monitor the shrinkage of tumors during RT and optimize the clinical target volumes accordingly. Our results also showed that this MR-guided dose adaptation technique has a dosimetric advantage over the standard of care and was associated with a reduction in normal tissue doses that translated into a reduction of the odds of long-term RT-induced toxicity. In the second aim, we used quantitative MRIs to determine its benefit for prediction of oncologic outcomes and characterization of RT-induced normal tissue toxicity. Our findings showed that delta changes of apparent diffusion coefficient parameters derived from diffusion-weighted images at mid-RT can be used to predict local recurrence and recurrence free-survival. We also showed that Ktrans and Ve vascular parameters derived from dynamic contrast-enhanced MRIs can characterize the mandibular areas of osteoradionecrosis. In the final clinical aim, we used CT images of recurrence and baseline CT planning images to develop a methodology and workflow that involves the application of deformable image registration software as a tool to standardize image co-registration in addition to granular combined geometric- and dosimetric-based failure characterization to correctly attribute sites and causes of locoregional failure. We then successfully applied this methodology to identify the patterns of failure following postoperative and definitive IMRT in HNC patients. Using this methodology, we showed that most recurrences occurred in the central high dose regions for patients treated with definitive IMRT compared with mainly non-central high dose recurrences after postoperative IMRT. We also correlated recurrences with pretreatment FDG-PET and identified that most of the central high dose recurrences originated in an area that would be covered by a 10-mm margin on the volume of 50% of the maximum FDG uptake. In the translational component of this work, we integrated radiomic features derived from pre-RT CT images with whole-genome measurements using TCGA and TCIA data. Our results demonstrated a statistically significant associations between radiomic features characterizing different tumor phenotypes and different genomic features. These findings represent a promising potential towards non-invasively tract genomic changes in the tumor during treatment and use this information to adapt treatment accordingly. In the final project of this dissertation, we developed a high-throughput approach to identify effective systemic agents against aggressive head and neck tumors with poor prognosis like anaplastic thyroid cancer. We successfully identified three candidate drugs and performed extensive in vitro and in vivo validation using orthotopic and PDX models. Among these drugs, HDAC inhibitor and LBH-589 showed the most effective tumor growth inhibition that can be used in future clinical trials

Incorporating Deep Learning Techniques into Outcome Modeling in Non-Small Cell Lung Cancer Patients after Radiation Therapy

Radiation therapy (radiotherapy) together with surgery, chemotherapy, and immunotherapy are common modalities in cancer treatment. In radiotherapy, patients are given high doses of ionizing radiation which is aimed at killing cancer cells and shrinking tumors. Conventional radiotherapy usually gives a standard prescription to all the patients, however, as patients are likely to have heterogeneous responses to the treatment due to multiple prognostic factors, personalization of radiotherapy treatment is desirable. Outcome models can serve as clinical decision-making support tools in the personalized treatment, helping evaluate patients’ treatment options before the treatment or during fractionated treatment. It can further provide insights into designing of new clinical protocols. In the outcome modeling, two indices including tumor control probability (TCP) and normal tissue complication probability (NTCP) are usually investigated. Current outcome models, e.g., analytical models and data-driven models, either fail to take into account complex interactions between physical and biological variables or require complicated feature selection procedures. Therefore, in our studies, deep learning (DL) techniques are incorporated into outcome modeling for prediction of local control (LC), which is TCP in our case, and radiation pneumonitis (RP), which is NTCP in our case, in non-small-cell lung cancer (NSCLC) patients after radiotherapy. These techniques can improve the prediction performance of outcomes and simplify model development procedures. Additionally, longitudinal data association, actuarial prediction, and multi-endpoints prediction are considered in our models. These were carried out in 3 consecutive studies. In the first study, a composite architecture consisting of variational auto-encoder (VAE) and multi-layer perceptron (MLP) was investigated and applied to RP prediction. The architecture enabled the simultaneous dimensionality reduction and prediction. The novel VAE-MLP joint architecture with area under receiver operative characteristics (ROC) curve (AUC) [95% CIs] 0.781 [0.737-0.808] outperformed a strategy which involves separate VAEs and classifiers (AUC 0.624 [ 0.577-0.658]). In the second study, composite architectures consisted of 1D convolutional layer/ locally-connected layer and MLP that took into account longitudinal associations were applied to predict LC. Composite architectures convolutional neural network (CNN)-MLP that can model both longitudinal and non-longitudinal data yielded an AUC 0.832 [ 0.807-0.841]. While plain MLP only yielded an AUC 0.785 [CI: 0.752-0.792] in LC control prediction. In the third study, rather than binary classification, time-to-event information was also incorporated for actuarial prediction. DL architectures ADNN-DVH which consider dosimetric information, ADNN-com which further combined biological and imaging data, and ADNN-com-joint which realized multi-endpoints prediction were investigated. Analytical models were also conducted for comparison purposes. Among all the models, ADNN-com-joint performed the best, yielding c-indexes of 0.705 [0.676-0.734] for RP2, 0.740 [0.714-0.765] for LC and an AU-FROC 0.720 [0.671-0.801] for joint prediction. The performance of proposed models was also tested on a cohort of newly-treated patients and multi-institutional RTOG0617 datasets. These studies taken together indicate that DL techniques can be utilized to improve the performance of outcome models and potentially provide guidance to physicians during decision making. Specifically, a VAE-MLP joint architectures can realize simultaneous dimensionality reduction and prediction, boosting the performance of conventional outcome models. A 1D CNN-MLP joint architecture can utilize temporal-associated variables generated during the span of radiotherapy. A DL model ADNN-com-joint can realize multi-endpoint prediction, which allows considering competing risk factors. All of those contribute to a step toward enabling outcome models as real clinical decision support tools.PHDApplied PhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162923/1/sunan_1.pd

Face recognition in the wild.

Research in face recognition deals with problems related to Age, Pose, Illumination and Expression (A-PIE), and seeks approaches that are invariant to these factors. Video images add a temporal aspect to the image acquisition process. Another degree of complexity, above and beyond A-PIE recognition, occurs when multiple pieces of information are known about people, which may be distorted, partially occluded, or disguised, and when the imaging conditions are totally unorthodox! A-PIE recognition in these circumstances becomes really “wild” and therefore, Face Recognition in the Wild has emerged as a field of research in the past few years. Its main purpose is to challenge constrained approaches of automatic face recognition, emulating some of the virtues of the Human Visual System (HVS) which is very tolerant to age, occlusion and distortions in the imaging process. HVS also integrates information about individuals and adds contexts together to recognize people within an activity or behavior. Machine vision has a very long road to emulate HVS, but face recognition in the wild, using the computer, is a road to perform face recognition in that path. In this thesis, Face Recognition in the Wild is defined as unconstrained face recognition under A-PIE+; the (+) connotes any alterations to the design scenario of the face recognition system. This thesis evaluates the Biometric Optical Surveillance System (BOSS) developed at the CVIP Lab, using low resolution imaging sensors. Specifically, the thesis tests the BOSS using cell phone cameras, and examines the potential of facial biometrics on smart portable devices like iPhone, iPads, and Tablets. For quantitative evaluation, the thesis focused on a specific testing scenario of BOSS software using iPhone 4 cell phones and a laptop. Testing was carried out indoor, at the CVIP Lab, using 21 subjects at distances of 5, 10 and 15 feet, with three poses, two expressions and two illumination levels. The three steps (detection, representation and matching) of the BOSS system were tested in this imaging scenario. False positives in facial detection increased with distances and with pose angles above ± 15°. The overall identification rate (face detection at confidence levels above 80%) also degraded with distances, pose, and expressions. The indoor lighting added challenges also, by inducing shadows which affected the image quality and the overall performance of the system. While this limited number of subjects and somewhat constrained imaging environment does not fully support a “wild” imaging scenario, it did provide a deep insight on the issues with automatic face recognition. The recognition rate curves demonstrate the limits of low-resolution cameras for face recognition at a distance (FRAD), yet it also provides a plausible defense for possible A-PIE face recognition on portable devices

Tensor based multichannel reconstruction for breast tumours identification from DCE-MRIs

A new methodology based on tensor algebra that uses a higher order singular value decomposition to perform three-dimensional voxel reconstruction from a series of temporal images obtained using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is proposed. Principal component analysis (PCA) is used to robustly extract the spatial and temporal image features and simultaneously de-noise the datasets. Tumour segmentation on enhanced scaled (ES) images performed using a fuzzy C-means (FCM) cluster algorithm is compared with that achieved using the proposed tensorial framework. The proposed algorithm explores the correlations between spatial and temporal features in the tumours. The multi-channel reconstruction enables improved breast tumour identification through enhanced de-noising and improved intensity consistency. The reconstructed tumours have clear and continuous boundaries; furthermore the reconstruction shows better voxel clustering in tumour regions of interest. A more homogenous intensity distribution is also observed, enabling improved image contrast between tumours and background, especially in places where fatty tissue is imaged. The fidelity of reconstruction is further evaluated on the basis of five new qualitative metrics. Results confirm the superiority of the tensorial approach. The proposed reconstruction metrics should also find future applications in the assessment of other reconstruction algorithms