Title: Dose Optimization for Pediatric Renal SPECT Imaging
Abstract: Like any real-world problem, the design of an imaging system always requires tradeoffs. For medical imaging modalities using ionization radiation, a major tradeoff is between diagnostic image quality (IQ) and risk to the patient from absorbed radiation dose. In nuclear medicine, reducing the radiation dose to the patient will always result in increased Poisson noise in the image. At the same time, reducing the radiation dose (RD), below some level at least, will always result in reduced risk of adverse effects to the patient. The overall goal of this research is to propose a rigorous IQ-RD tradeoff analysis method for pediatric nuclear medicine renal imaging. However, the methodologies developed in this proposal can also be applied to other nuclear medicine imaging applications and other important medical modalities involving ionization radiation such as computed tomography and planar X-rays.
Balancing the tradeoffs between RD and IQ is especially important for children, as they are often considered more vulnerable to radiation than adults. In nuclear medicine imaging, reducing the RD requires reducing the administered activity (AA). Lower AA results in increased Poisson noise in the images or requires longer acquisition durations to maintain the noise level. In pediatric nuclear medicine, it is desirable to use the lowest AA and the shortest acquisition duration that gives sufficient IQ for clinical diagnosis. In current clinical practice, AA for pediatric molecular imaging is often based on the North American consensus guidelines (U.S.) and the European pediatric dosage card (Europe). Both of these dosing guidelines involve scaling the adult AA by patient weight subject to upper and lower constraints on the AA. However, these guidelines were developed based on expert consensus or rough estimates (estimated count rates) of IQ rather than rigorous, objective measures of performance on the diagnostic task.
In this research, we propose a general framework for optimizing RD with task-based assessment of IQ. Here, IQ is defined as an objective measure of the user performing the diagnostic task that the images were acquired to answer. Specifically, we propose to establish relationships between AA, acquisition duration, measures of body habitus, and IQ for pediatric patients undergoing renal molecular imaging procedures. To investigate IQ as a function of renal defect detectability, we have developed a projection image database modeling imaging of 99mTc-DMSA, a renal function agent. The database uses a highly-realistic population of pediatric phantoms with anatomical and body morphological variations. Using the developed projection image database, we have explored patient factors that affect IQ and are currently in the process of determining relationships between IQ and AA (IQ-AA curve) in terms of these found factors. Our preliminary data have shown that the current weight-based guidelines, based on scaling the AA by patient weight, are not optimal in the sense that they do not give the same image quality for patients with the same weight. Furthermore, we have found that factors that are more local to the target organ may be more robust than weight for estimating the AA needed to provide a constant IQ across a population of patients. In the case of renal imaging, we have discovered that girth is more robust than weight in predicting AA needed to provide a desired IQ. In addition, in order to simulate a full clinical multi-slice detection task (just like what a nuclear medicine physician would do), we propose to develop a CNN-based model observer. We will perform human observer studies to verify and calibrate the developed model observers used to generate the IQ-AA curves. The results of this proposal will provide the data needed by standards bodies to develop improved dosing guidelines for pediatric molecular imaging that result in more consistent image quality and absorbed dose.
Title: Applications of high-speed optical signal processing in high-dimensional data acquisition
Abstract: Thanks to large bandwidth, and the ability to capture large amount of information in parallel, optical technologies have transformed the way we capture, process, and communicate information. During this talk I will discuss how optical signal processing can be used in conjunction with novel data compression strategies in order to break the decades long bottleneck faced by electronic systems. I will particularly discuss utility of optical signal processing on big data applications ranging from high speed material characterization, to capturing neural signals over large volume at unprecedented depth and speed.
During the first half of this talk I will discuss how we are taking advantage of parallel image acquisition techniques in order to gain a deeper understanding of rapidly evolving combustion events over a broad spectral range. Despite the rich body of scientific research, the volatile nature of the combustion process has presented an obstacle to our understanding of the chemical kinetics involved in flame propagation and evolution. Many combustive reactions occur in the sub mili-second time scale and involve high velocity motion and interaction of fuel reagents. Hyperspectral imaging technologies are an attractive solution which combine high spatial resolution with fine spectral resolution. However, most conventional hyperspectral cameras rely on slow scanning mechanisms and therefore are ill-suited for capturing fast evolving events. The emergence of Compressive Sensing (CS) over the past decade, has opened the doors to acquiring high dimensional signals at high speed. In the first part of this talk I will discuss how novel optical techniques can be combined with CS algorithms to realize Mega Frame hyperspectral imaging platforms for material diagnostics.
The second portion of my talk will focus on high spatio-temporal neural recording applications. Multi-photon microscopy has been a major breakthrough in overcoming optical scattering when imaging individual neurons deep inside the brain of live animals. Despite the impressive image quality and robustness to scattering, point scanning multi-photon microscopes face a fundamental trade-off between the field of view (FOV) and imaging speed. Higher speed, volumetric multi-photon imaging and stimulation technologies have the potential to revolutionize monitoring of neural network activity in vivo. In this part I will discuss our efforts to develop a scalable, volumetric, two-photon neural recording technology that combines rapid, volumetric scanning of a wide illumination field with synchronized high-resolution dynamic spatial patterning within the illumination field. This approach will allow us to both rapidly address large volumes and also achieve high-resolution random access within the sub-regions of the scan. We will leverage the random access capabilities of this hardware to implement compressive and adaptive imaging strategies that maximize the image information acquired for a given time and laser energy.
Title: Modeling Cellular Events: Chemotaxis and Aneuploidy
Abstract: Biology is the ‘study of complex natural things’ and the biologists are mostly interested in details of those complexity in a system. But often a simpler mathematical model is proved to be very efficient in deciphering the underlying basic working principle of the system. Despite the usefulness, these models are often criticized for not being able to explain the sufficient details of the wide range of experimental observations of different cases of pharmacological/genetic perturbations.
Title: Control of pattern formation in excitable systems
Abstract: Pattern formation embodies the beauty and complexity of nature. Some patterns like traveling and rotating waves are dynamic, while others such as dots and stripes are static. Both dynamic and static patterns have been observed in a variety of physiological and biological processes such as rotating action potential waves in the brain during sleep, traveling calcium waves in the cardiac muscle, static patterns on the skins of animals, and self-regulated patterns in the animal embryo. Excitable systems represent a class of ultrasensitive systems that are capable of generating different kinds of patterns depending on the interplay between activator and inhibitor dynamics. Through manipulation of different excitable parameters, a diverse array of traveling wave and standing wave patterns can be obtained. In this thesis, I use pattern formation theory to control the excitable systems involved in cell migration and neuroscience to alter the observed phenotype, in an attempt to affect the underlying biological process.
Cell migration is critical in many processes such as cancer metastasis and wound healing. Cells move by extending periodic protrusions of their cortex, and recent years have shown that the cellular cortex is an excitable medium where waves of biochemical species organize the cellular protrusion. Altering the protrusive phenotype can drastically alter cell migration — that can potentially affect critical physiological processes. In the first part of this thesis, I use excitable wave theory to model and predict wave pattern changes in amoeboid cells.
Excitable systems originated in neuroscience, where different patterns of activity reflect different brain states. Sleep is associated with slow waves, while repeated high-frequency waves are associated with epileptic seizures. These patterns arise from the interplay between the cerebral cortex and the thalamus, which form a closed-loop architecture. In the second part of this thesis, I use a three-layer two-dimensional thalamocortical model, to explore the different parameters that may influence different spatio-temporal dynamics on the cortex.
Title: Extending the potential of thin-film optoelectronics via optical and photonic engineering
Project summary: Thin-film optoelectronics using solution-processed materials have become a strong research focus in recent decades. These technologies have demonstrated convenience and versatility, due to their solution-processed nature, in a wide range of applications such as solar power harvesting, photodetection, light emitting devices and even lasing. Some of the variants of these materials also enabled and dominate the field of flexible electronics, especially for display technologies, achieving large-scale industrialization and commercialization years ago specifically in applications where their conventional counterparts – bulk semiconductors – are limited. The development of optoelectronics applications using organic materials, colloidal quantum dots, perovskites, etc., has been made possible by research progress in materials and chemical engineering of the active material itself, as well as in optical and photonic engineering in the device architecture and related structures. The focus of this project is mainly on the latter set of approaches applied to lead chalcogenide-based colloidal quantum dot thin films.
Colloidal quantum dots (CQDs) are a type of semiconductor material in the form of nanocrystals (1-10 nm in diameter) of the corresponding bulk material. The spatial confinement of electrons and holes leads to significantly reconstructed energy band structures. Usually this manifests as a series of discrete energy levels above or below the corresponding bulk conduction and valence band edges, instead of the corresponding semi-continuum of states observed in bulk semiconductors. The spacings between the discrete energy levels are highly dependent on the size of the quantum dots, which at the same time determines the properties of optical transitions responsible for absorption (Figure 1b), modulation of the refractive index, etc. In this sense, CQDs are considered “tunable” by controlling the ensemble so that it predominantly consisting CQDs of one desired shape and size.
CQDs are solution-processed materials. The processing of CQDs starts from synthesis using solutions containing metal-organic precursors. The controlled growth of nanocrystals results in a dispersion of pristine CQDs in certain solvents. After that, the CQDs are purified and chemically treated to modify their surface ligands, through a series of precipitation, redispersion, phase transfer and concentration steps. The deposition of films of CQDs onto desired substrates is achieved by solution-compatible techniques such as spin-casting, blade coating and screen printing. A functional CQD film is usually 10-500 nm thick depending on its application and is usually preceded and/or succeeded by the deposition of other electronically functional device layers.
Lead sulfide (PbS) CQDs are widely used for applications involving solar photon absorption and resulting energy conversion. In the example of a CQD solar cell, PbS CQDs with effective band gaps of 1.3 eV are chosen as the active material. The full device utilizes a p-n or p-i-n structure, and a typical device architecture consists of a transparent conductive oxide (TCO) electrode layer, an electron transport layer (ETL), the absorbing PbS CQD film, a hole transport layer (HTL) and metal top electrode. Similar structures are also used in photodetectors and light emitting diodes, with critical layers substituted.
For the first section of the project, we studied and exploited the color reproduction capabilities using reflective interference from CQD solar cells, while maintaining high photon absorption and current generation. The second section is aimed at exploring the possibility of simultaneously controlling the spectral reflection, transmission and absorption of thin film optoelectronics using embedded photonic crystal structures in CQD films and other highly absorptive materials. In the third section, we devised and built a 2D multi-modal scanning characterization system for spatial mapping of photoluminescence (PL), transient photocurrent and transient photovoltage from a realistically large device area with micron-resolution. The last section of the project focuses on economical and scalable solar concentration solutions for CQD and other thin film solar cells.
We mostly limit our discussion and demonstration to PbS CQD solar cells within the
scope of this proposal; however, it is worth pointing out that the techniques and
principles described below could be applied to most optoelectronic materials that share
the solution-compatible deposition and processing procedures.
Title: New Diagnostic and Therapeutic Tools for Intravascular Magnetic Resonance Imaging (IVMRI)
Abstract: Intravascular (IV) magnetic resonance imaging (IVMRI) is a developing technology that uses minimally-invasive MRI coils to guide diagnosis and treatment. The combination of signal-to-noise (SNR) enhancement from the microscopic MRI local coils and the multi-contrast mechanisms provided by MRI has enlarged the possibilities of high-resolution imaging-guided diagnosis and treatment of atherosclerosis and nearby or surrounding cancers. Recent years have seen the development of many advanced MRI techniques including MRI thermometry and real-time MRI, yet the development of procedures that apply these advances to intravascular MRI remain challenging.
Among interventional diagnostic techniques, MRI endoscopy is an IVMRI technique that transfers MRI from the laboratory frame-of-reference to the IV-coil’s frame-of-reference. This enables high-resolution MRI of blood vessels with endoscopic-style functionality. Prior MRI endoscopy work was limited to ~2 frames-per-second (fps), which is not real-time and potentially limiting in clinical applications. Improving the speed of MRI endoscopy further without excessive undersampling artifacts could enable the rapid deployment and advancement of an IVMRI endoscope entirely by MRI guidance to evaluate local, advanced, intra- and extra-vascular disease at high resolution using MRI’s unique multi-contrast and multi-functional assessment capabilities. Furthermore, with its unique capability in high-resolution thermometry, IVMRI is suitable to guide and monitor ablation therapy delivery in disease such as vessel-involving cancers. Prior work using an IVMRI loopless antenna for both MRI and radiofrequency ablation (RFA) was limited in precision and ablated only the tissue in direct contact with the probe. Thus, one goal is to extend IVMRI methods using state-of-the-art real-time MRI acceleration methods to provide MRI endoscopy at a speed comparable to that of existing catherization and optical endoscopy procedures.
A second goal is to provide a minimally-invasive, IV-accessed ablation technology that could provide precision localization and perivascular ablation to render resectable, an otherwise inaccessible or non-resectable cancer with vascular involvement.
To these ends, a Max-Planck Institute (MPI) real-time MRI system employing graphic processing units (GPU) is first adapted to facilitate MRI endoscopy at 10 fps endoscopy with real-time display and is demonstrated in vitro and in vivo. To further improve image quality, we propose to use a neural network (CNN) trained on artifact patterns generated from motionless endoscopy to ameliorate artifacts during real-time imaging. A new method based on generative models and manifold learning is then proposed to optimize image contrast responsive to the varying endoscopic surroundings.
To address the second goal, an intravascular ultrasound ablation transducer is integrated with IVMRI to provide a tool that can also deliver therapy. By integrating an IV high-intensity ultrasound (HIFU) ablation component, the precision and depth of ablation is extended and contact injuries can be avoided. Procedures are developed to evaluate accuracy using ex vivo samples and feasibility is demonstrated in animals in vivo.
Title: Collaborative Regression and Classification via Bootstrapping
Abstract: In modern machine learning problems and applications, the data that we are dealing with have large dimensions as well as amount, making data analysis time-consuming and computationally inefficient. Sparse recovery algorithms are developed to extract the underlining low dimensional structure from the data. Classical signal recovery based on l1 minimization solves the least squares problem with all available measurements via sparsity-promoting regularization. It has shown promising performances in regression and classification. Previous work on Compressed Sensing (CS) theory reveals that when the true solution is sparse and if the number of measurements is large enough, then solutions to l1 converge to the ground truths. In practice, when the number of measurements is low or when the noise level is high or when measurements arrive sequentially in streaming fashion, conventional l1 minimization algorithms tend to struggle in signal recovery.
This research work aims at using multiple local measurements generated from resampling using bootstrap or sub-sampling to efficiently make global predictions to deal with aforementioned challenging scenarios in practice. We develop two main approaches – one extends the conventional bagging scheme in sparse regression from a fixed bootstrapping ratio whereas the other called JOBS applies a support consistency among bootstrapped estimators in a collaborative fashion. We first derive rigorous theoretical guarantees for both proposed approaches and then carefully evaluate them with extensive simulations to quantify their performances. Our algorithms are quite robust compared to the conventional l1 minimization, especially in the scenarios with high measurements noise and low number of measurements. Our theoretical analysis also provides key guidance on how to choose optimal parameters, including bootstrapping ratios and number of collaborative estimates. Finally, we demonstrate that our proposed approaches yield significant performance gains in both sparse regression and classification, which are two crucial problems in the field of signal processing and machine learning.
Title: Brain structure segmentation using multiple MRI pulse sequences
Abstract: Medical image segmentation is the process of delineating anatomical structures of interest in images. Automatic segmentation algorithms applied to brain magnetic resonance images (MRI) allow for the processing of large volumes of data for the study of neurodegenerative diseases. Widely-used segmentation software packages only require T1-weighted (T1-w) MRI and segment cortical and subcortical structures, but are unable to segment structures that do not appear in T1-w MRI. Other MRI pulse sequences have properties that allow for the segmentation of structures that are invisible (or barely discernible) in T1-w MRI.
In this dissertation, three novel medical image segmentation algorithms are proposed to segment the following structures of interest: the thalamus; the falx and tentorium; and the meninges. The common theme that connects these segmentation algorithms is that they use information from multiple MRI pulse sequences because the structures they target are nearly invisible in T1-w MRI. Segmentation of these structures is used in the study of neurodegenerative diseases such as multiple sclerosis and for the development of computational models of the brain for the study of traumatic brain injury.
Our automatic thalamus and thalamic nuclei segmentation algorithm extracts features from T1-w MRI, T2-w MRI, and diffusion tensor imaging (DTI) to train a random forest classifier. Using a leave-one-out cross-validation on nine subjects, our algorithm achieves mean Dice coefficients of 0.897 and 0.902 for the left and right thalami, respectively, which are higher Dice scores than the three state-of-art methods we compared against.
Our falx and tentorium segmentation algorithm uses T1-w MRI and susceptibility-weighted imaging (SWI) to register multiple atlases and fuse their boundary points to generate a subject-specific falx and tentorium. Our method is compared against single-atlas approaches and achieves the lowest mean surface distance of 0.86 mm and 0.99 mm to a manually delineated falx and tentorium, respectively.
Our meninges reconstruction algorithm uses T1-w MRI, T2-w MRI, and a synthetic computed tomography (CT) image generated via convolutional neural network to find two layers of the meninges: the subarachnoid space and dura mater. We compare our method with other brain extraction and intracranial volume estimation algorithms. Our method produces a subarachnoid space segmentation with a mean Dice score of 0.991, which is comparable to the top-performing state-of-art method, and produces a dura mater segmentation with a mean Dice score of 0.983, which is the highest among the compared methods.
Title: Minimally-Invasive Lens-free Computational Microendoscopy
Abstract: Ultra-miniaturized imaging tools are vital for numerous biomedical applications. Such minimally invasive imagers allow for navigation into hard-toreach regions and, for example, observation of deep brain activity in freely moving animals with minimal ancillary tissue damage. Conventional solutions employ distal microlenses. However, as lenses become smaller and thus less invasive they develop greater optical aberrations, requiring bulkier compound designs with restricted field-of-view. In addition, tools capable of 3-dimensional volumetric imaging require components that physically scan the focal plane, which ultimately increases the distal complexity, footprint, and weight. Simply put, minimally-invasive imaging systems have limited information capacity due to their given cross-sectional area.
This thesis explores minimally-invasive lens-free microendoscopy enabled by a successful integration of signal processing, optical hardware, and image reconstruction algorithms. Several computational microendoscopy architectures that simultaneously achieve miniaturization and high information content are presented. Leveraging the computational imaging techniques enables color-resolved imaging with wide field-of-view, and 3-dimensional volumetric reconstruction of an unknown scene using a single camera frame without any actuated parts, further advancing the performance versus invasiveness of microendoscopy.