Jonathan M. Links - US grants

We propose to significantly upgrade the image display, processing, and data analysis capabilities of The Johns Hopkins Positron Emission Tomography (PET) Facility. This Facility currently serves research involving three Program-Project grants and three individual project grants. These grants include, as investigators, adult and pediatric neurologists, psychiatrists, surgeons, and radiologists from six different departments. Our current image display and analysis capabilities are limited to two DEC PDP 11/60 computers, which are single tasking, limited in abilities, and no longer manufactured or supported. We propose to acquire a dedicated system consisting of five super microcomputers in a networked configuration, with custom software burned in PROMs. As detailed in this application, the proposed system will increase processing throughput, improve data base management, and permit the use of significantly more advanced analysis techniques.

Core C provides the instruments, techniques, personnel and expertise necessary for in vivo quantification of the distribution of radioactivity in large animals and human beings. This Core has three main types of activities: supervision of the performance of scans, development and implementation of new acquisition and image processing techniques, and collaboration with each Project in the optimization of acquisition and processing protocols. This Core contains the instrumentation, image processing workstations, techniques for data acquisition and processing, and the personnel responsible for the Core's operation.

DESCRIPTION (Adapted from Applicant's Abstract): Interest in dual-isotope imaging in nuclear medicine is growing, both for studies employing two tracers to simultaneously examine two different processes in a single organ, and for simultaneous transmission/emission imaging in SPECT. A major problem with all dual-isotope imaging is the "crosstalk" between the two isotopes (i.e., the contribution of one isotopes's counts into the other isotope s energy window). The long term goal of the proposed research is to improve the quantitative accuracy and precision of SPECT imaging in the setting of mild disease, where quantification is of most value. Toward that end, the applicants previously described the use of Fourier-based restoration filtering in (single-isotope) SPECT and PET to improve quantitative accuracy. They hypothesized that a significant extension of such filtering can be used in dual-isotope imaging to simultaneously (1) improve contrast in each isotope's "direct" image, (2) reduce image noise, and (3) reduce the crosstalk contribution from the other isotope. Based on the derivation described below, the applicants called such a filter a "vector Wiener filter." The applicants proposed a series of computer simulations and phantom experiments which mimic clinically mild brain and heart disease; specifically: Aim 1: To implement a two-dimensional shift-invariant vector Wiener filter for projection data, and a three-dimensional shift-invariant vector Wiener filter for reconstructed images, and to validate their quantitative accuracy in computer simulations, including realistic brain and cardiac imaging conditions; Aim 2: To assess the effects of vector Wiener filtering on accuracy and precision, in a series of dual-isotope phantom studies, including both dual-isotope brain and cardiac phantom studies, and simultaneous transmission/emission phantom studies; and Aim 3: To study implementation issues, including estimation of power spectral density, to derive a parametric form of the vector Wiener filter, and to derive and initially evaluate a shift-variant form of the filter.

DESCRIPTION (Provided by Applicant): The diagnostic and quantitative accuracy of cardiac SPECT are limited by depth-dependent blurring, attenuation, scatter, and image noise. Approaches to correct for these physical effects have been described, but are not widely used clinically, primarily due to lack of comprehensive validation. We propose to pooi the talents of leading investigators in nuclear cardiology to validate the most promising techniques, as follows: Aim 1. To utilize a rigorous implementation of OSEM that includes models of attenuation, collimator blur, and shift-variant scatter (Tsui and colleagues), with our own approach, which is less rigorous but has produced excellent human multi-center trial results, as a baseline for comparison. Aim 2. To assess the quantitative accuracy of these approaches in a series of computer simulations and actual phantoms: the MCAT and NCAT code to produce a series of simulations of different "defects" (in terms of location, size, and degree of "ischemia"), with varying degrees of attenuation, scatter, and blur, and the newest Data Spectrum cardiac phantom, which is capable of "beating." The "true" activity concentration in the object (i.e., the model prior to simulation) or phantom will serve as the baseline for comparison. Aim 3. To assess the quantitative accuracy of these approaches in a series of dog studies with a model of experimentally-induced ischemia via variable coronary artery occlusion, with different ischemic regions (in terms of location and severity). The true distribution of myocardial perfusion, as measured by microspheres counted ex vivo, will serve as the baseline for comparison. Aim 4. To assess the effects of these approaches on the diagnostic accuracy of visual interpretation and polar-plot quantification of human multi-center clinical SPECT studies in the diagnosis of coronary artery disease. The results of coronary angiography will serve as the baseline for comparison. Hypotheses: The OSEM approach will have significantly better diagnostic and quantitative accuracy than other approaches, clinically important in magnitude, especially in mild disease patients.

[unreadable] DESCRIPTION (provided by applicant): This is a P01 application in response to FOA RFA-TP-08-001; it focuses on mental and behavioral public health systems research in preparedness and emergency response. The application consists of a research core and four inter-related projects. The Research Core will provide project and administrative grant management. It will also support new research initiatives in the form of new investigator and pilot project funding (beyond the four proposed research projects). The four research projects themselves are heavily interrelated and synergistic. They represent different elements of a unifying organizational paradigm based on the 3 phases of an emergency: pre-event, event, and post-event, and a unifying theoretical paradigm, the Extended Parallel Processing Model. The application explicitly targets three of the major components of the public health system: (1) Government Public Health Infrastructure, (2) the Media, and (3) Communities (specific elements thereof) - The major goal of our proposed research is to build the capacity, competency, and coordination of the public health system to prepare for and respond to mental and behavioral health aspects of emergencies. Our research seeks to identify and mitigate deficiencies in organization, pre-conditioning, breadth of response capacity, competency, and coordination, and the legal environment, with a specific focus on mental and behavioral health issues. The four projects are Project #1: Applying the Extended Parallel Process Model to Willingness-to-Respond in the Public Health System; Project #2: Fostering Coordinated Mental Health Preparedness Planning; Project #3: Role of the Media in Resistance; and Project #4: Legal and Ethical Assessment Concerning Mental and Behavioral Health Preparedness. [unreadable] [unreadable] In emergencies and disasters that have occurred to date, psychological "casualties" outnumber physical casualties by as much as 100:1, yet our public health system are woefully unprepared to handle them. The four projects, new investigator and pilot project programs, together, will significantly enhance the capacity, competency, and coordination of the public mental health system in times of emergency. [unreadable] [unreadable] [unreadable]

This Nanotechnology Undergraduate Education (NUE) in Engineering program entitled, New Undergraduate Engineering Minor in Nanotechnology Risk Assessment and Public Policy, at the Johns Hopkins University, under the direction of Dr. Justin Hanes, will create a new undergraduate minor entitled, Nanotechnology Risk Assessment and Public Policy. The minor will represent a collaboration between multiple departments in the Whiting School of Engineering, the Bloomberg School of Public Health, and the Hopkins Berman Institute of Bioethics. The minor represents an interdisciplinary approach to the training of undergraduate students in the basics of nanotechnology risk assessment (including both the environment/ecosystem and human health), legal and ethical issues, and public policy implications.

The proposal for this awrad was received in response to the Nanotechnology Undergraduate Education (NUE) in Engineering Program Solicitation (NSF 07-554) and is being co-funded by the Division of Social and Economic Sciences (SES) in the Directorate for Social, Behavioral and Economic Sciences (SBE), and the Division of Engineering Education and Centers (EEC) in the Directorate for Engineering (ENG).

DESCRIPTION (provided by applicant): This application describes a new center - the Johns Hopkins Preparedness and Emergency Response Learning Center (JH-PERLC) - that will be created, if funded, in response to FOA CDC-RFA-TP10-1001. The proposed PERLC consists of three parts - A, B, and C - that cover core competency-based training for the workforce, partner-requested education and training, and program core and network activities, respectively. The entire application is based on two parallel frameworks, one that covers our pedagogic approach and the other that covers our content approach. The pedagogic approach is based on Anderson and Krathwohl's revision of Bloom's Taxonomy. Bloom and Anderson and Krathwohl focus on learning objectives, whereas the current FOA and the associated CDC/ASPH Preparedness and Response Core Competencies development project focus on competencies, but learning objectives that correspond to competencies can be directly developed once the competencies are articulated. Bloom identified six levels within the cognitive domain, from the simple recall or recognition of facts at the lowest level, through increasingly more complex and abstract cognitive levels, to evaluation at the highest level. Anderson and Krathwohl extended Bloom's Taxonomy to current educational practices;their Taxonomy Table is a matrix: The horizontal dimension is the cognitive process dimension, and contains six (cognitively-escalating) categories;the vertical dimension is the knowledge dimension, and contains four (micro-to-macro) knowledge categories. The content approach is based on a new framework of ours - Ready, Willing, and Able - that represents a simple, easily understandable framework for planning, implementing, and evaluating efforts to ensure high-quality individual and organizational responses to public health emergencies. We conceptualize our practice partners in two ways: (1) those with whom we now work and hope to continue to work who mainly receive our trainings and services;our area of service is Maryland, Delaware, and DC, although we cover the entire country;(2) those with whom we more intensively collaborate in the design, development, and evaluation of core competency-based training;these key partners are Montgomery County Health Department, Multnomah County Health Department, and Seattle &King County Health Department. These three health departments are 3 of the 8 current NACCHO Advanced Practice Centers. We propose to continue our current practice of utilizing multiple delivery venues, including face-to-face, online, and hybrid approaches. Evaluation will be based on metrics that are "SMART:" specific, measureable, achievable, realistic, and time-phased, and the evaluation will consider structures, processes, and outcomes (i.e., not just outcomes). We propose to continue to use the logic model and associated evaluation approach we first described in our original CPHP application. We intend to continue to "build the evidence base" for competency-based preparedness training, by publishing evidence in the peer-reviewed literature regarding the efficacy of training (e.g., from our evaluation activities), as well as publishing descriptions of novel training approaches. The staff for our proposed PERLC will include a PI, center coordinator, full-time instructional designer, full-time-equivalent e-learning specialist, full-time evaluator, and a cadre of experienced subject-matter-experts, who will act as curricular content developers and trainers, covering all competency domains.

DESCRIPTION (provided by applicant): Single-Photon Emission Computed Tomography plays an important and well- validated role in the diagnosis and staging of a number of important cardiac diseases, and is widely used and available at many clinical sites in the US and around the world. The most common application has been myocardial perfusion SPECT to evaluate cardiovascular disease. A new and potentially important application is I-123 MIBG SPECT (AdreView) for myocardial innervation imaging. While there has been a great deal of work to develop improved reconstruction methods, and some work to develop optimized instrumentation and acquisition parameters, these have been done largely in isolation of each other. Questions such as: what is the optimal collimator when using collimator response compensation? what is the optimal energy window with scatter compensation?, is it optimal to use the same acquisition time for each projection view?, and is it optimal to use the same acquisition time per patient? have never been addressed. In addition, there are currently a number of dedicated scanners for cardiac imaging that incorporate several novel features to decrease acquisition time. Some of these are based on cadmium zinc telluride semiconductor detectors that provide improved full-width at half maximum energy resolution, but have a more complicated energy response that includes tails extending to low-energies. Other new detector materials such as LaBr with improved energy resolutions are on the horizon. However, energy windows and scatter compensation methods for CZT and LaBr detectors have not been optimized, nor has their benefit on cardiac imaging been rigorously tested. In this grant we propose to use novel, state-of-the art task-based image quality measures and realistic well-validated simulations calibrated by clinical studies to perform comprehensive end-to-end optimization of instrumentation, acquisition, reconstruction, and compensation parameters and methods. We will investigate the tradeoff between these factors and acquisition time/injected dose, allowing physicians to trade image quality for reduced radiation dose. The results would have an immediate impact in providing improved image quality, diagnostic accuracy, and reduced patient dose, while also having a longer term impact by guiding the development of future SPECT systems. The work will also provide validation of novel optimization strategies using projection-domain ideal-observers that handle mismatch between the imaging model used in the reconstruction and the true imaging process.