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: 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: 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.