Xiaohong J. Zhou - US grants

[unreadable] DESCRIPTION (provided by applicant): Magnetic resonance (MR) imaging and spectroscopy at high magnetic field (greater than or equal to 3.0 Tesla) is one of the fastest growing areas in biomedical imaging. Recent developments in high-field MR provide unprecedented research opportunities in molecular imaging, metabolic mapping, functional imaging, cellular imaging, and other exciting areas. Recognizing the need to stimulate and enhance discussions on the technical developments and new applications of high-field MR, two Study Groups (High-Field Systems and Applications Study Group, and MR Engineering Study Group) of the International Society of Magnetic Resonance in Medicine (ISMRM) have decided to organize jointly a workshop on "Advances in High-Field Magnetic Resonance Imaging and Spectroscopy". This Workshop will be held in Berkeley, California in October, 2006. The objectives of the Workshop are: (1) to review recent engineering and physics advances in high-field MR; (2) to discuss the emerging applications of high- field MR, as well as the future directions; (3) to provide a forum to foster interdisciplinary collaborations; and (4) to educate the up-coming basic and clinical scientists and promote their participation in high- field MR research. This R13 grant application is directed towards achieving the last objective of the Workshop. In the proposed project, an educational stipend program will be created to provide support for twenty (20) trainees to attend the Workshop. The trainees will include students, postdoctoral fellows, and residents who are working in the area of high-field magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), molecular imaging, or other related areas. Special effort will be made to support women, racial/ethnic minorities, persons with disabilities, and other groups who are underrepresented in science, engineering, or medicine. Successful completion of the proposed project will provide an opportunity for the up-coming basic and clinical scientists to be exposed to the latest development in high-field MRI and MRS, and allow them to take on the technical challenges of high- field MR and explore its ever-expanding applications. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The University of Illinois at Chicago (UIC) requests grant support to purchase a state-of-the- art whole-body 3 Tesla (3T) magnetic resonance imaging (MRI) scanner to perform advanced anatomic, functional, spectroscopic and physiologic imaging for biomedical research. The requested 3T MRI scanner is urgently needed to (a) accommodate a rapidly increasing number of NIH-funded projects, (b) replace an early generation, out-dated, un-upgradable 3T scanner with cutting-edge 3T technologies, and (c) establish the first-ever 3T imaging facility dedicated to research at UIC. The proposed 3T scanner is of paramount importance for UIC to sustain and strengthen its position at the forefront of imaging technology and to ensure successful completion of fifteen active NIH-funded projects (eleven R01's, one P50, one R21, one K24, and one R03) with a total award of $32.6M. The state-of-the-art MRI scanner will also play a pivotal role in our future expansion from brain to body imaging over a broad range of basic, translational, and clinical research areas. Overall, there is a compelling need for a high-end 3T scanner dedicated to research at UIC. The instrumentation requested is a 3T General Electric Discovery MR750 scanner with advanced neuro- and body-imaging capabilities enabled by cutting-edge technologies. The 3T scanner will be utilized as a University-wide resource located in the College of Medicine. At least 2,500 square feet of space is allocated by the University to house the new 3T MRI facility. Substantial infrastructure and technical expertise are already in place for installing, operating and maintaining the 3T scanner. More importantly, UIC and its College of Medicine have committed $1.17M to the proposed new 3T facility to cover space renovation, site preparation, scanner installation, and operation costs. To ensure continued successful operation in the post-award period, a Project Review Committee will be created to allocate the 3T resource according to the NIH guidelines and promote equipment usage while ensuring scientific merit and productivity. In addition, an Advisory Committee will be created to oversee the management of this grant and make policy and strategic decisions. This administrative structure is accompanied by a financial plan that ensures self-supporting in the post-award period. The mission of our 3T imaging facility is to promote the development and synergistic application of MRI techniques to a broad range of biomedical disciplines. The purchase of the new 3T scanner is a critical and significant step to accomplish this mission.

ABSTRACT Biological tissues are heterogeneous, particularly at a microscopic scale (e.g., ~10?m). The degree of tissue heterogeneity plays a very important role in tissue characterization, disease diagnosis, and monitoring treatment efficacy. In cancer, for example, intra-tumor heterogeneity has been identified as one of the most important factors in cancer staging and individualized treatment, as demonstrated in a number of recent papers in high-impact journals. Tissue heterogeneity arises from a variety of origins, such as genetics, epigenetics, physiology, and pathology, all of which lead to structural heterogeneity at a specific spatial scale. Studying tissue structural heterogeneity, therefore, can provide a unique avenue to probe the underlying biological processes. Current spatial resolution for human MRI, unfortunately, is far from adequate to visualize tissue structural heterogeneity at a microscopic level (e.g., ~5-50 ?m). Efforts to further improve the resolution face formidable technical challenges. An alternative strategy is to use the present spatial resolution, but focus on extracting sub-voxel information by linking a macroscopic voxel-level measurement to a microscopic intra-voxel physical process that reflects tissue structural heterogeneity. Using a novel diffusion model based on fractional order calculus (FROC), our group, echoed by others, has observed an increasing number of evidences suggesting a link between a macroscopic diffusion parameter and microscopic intra-voxel tissue heterogeneity. The overarching goal of the proposed project is to further develop and validate this promising diffusion imaging technique, and demonstrate that a set of FROC parameters can enable characterization of intra-voxel tissue heterogeneity in human subjects. The scientific premise of the project is that microstructural heterogeneity is an important tissue feature and that advanced diffusion MRI based on the FROC model can non-invasively assess microstructural heterogeneity, leading to new imaging markers. Our central hypothesis is that diffusion behavior in tissues at high b-values can be characterized by a heterogeneous diffusion process, and the degree of diffusion heterogeneity can be directly linked to intra-voxel tissue structural heterogeneity. The project has four Specific Aims. First, we will optimize a high-resolution diffusion imaging technique to enable accurate measurement of intra-voxel diffusion heterogeneity. Second, we will generalize the FROC diffusion model to account for intra-voxel diffusion heterogeneity not only spatially but also temporally. Third, using the techniques in the first two aims, we will demonstrate the possible relationship between MRI-based intra-voxel diffusion heterogeneity and histology-based structural heterogeneity on postmortem human brains with glioma. Finally, we will extend the demonstration to in vivo studies on sixty brain tumor patients using stereotactic biopsies. Taking together, the project will address a significant unmet need that is of great importance in biological sciences and clinical medicine, especially cancer.

Project Summary/Abstract Osteoarthritis (OA) is the single most important cause of disability in mid and late life. About 27 million people in the United States suffer from this incurable process and 10 million have OA of the knee. Total knee arthroplasty (TKA) is a reliable treatment option for patients disabled by knee OA who have failed nonoperative treatment, with 58% of these surgeries being performed on patients 65 years or older. TKA surgeries were performed on more than 700,000 patients in the United States in 2012 and estimates expect this number to increase between 143% and 565% by 2050. Most patients experience pain relief within 6 to 12 weeks following TKA; however, 8 to 34% of patients experience chronic postsurgical pain, defined by the International Association for the Study of Pain as clinically important pain lasting more than 3 months after surgery, with limited improvement in functional outcomes often despite an uneventful surgical course and a satisfactory radiographic appearance. With one projected estimate of 3.48 million TKA surgeries per year in the USA by 2030, up to 500,000 patients annually could develop chronic pain following TKA. The objective of this project is to aid in the construction of a dataset that encompasses clinical, biological (omics), psychological, socioeconomical and imaging predictors for a diverse group of patients undergoing TKA. Rush University the largest provider of joint replacement surgery in Illinois, performing 2,100 TKA procedures in 2017. With our Institute for Translational Medicine (ITM) partners, the University of Chicago, and NorthShore University Health System our NCATS CTSA-funded program hub has extensive translational research expertise and serves a diverse patient population (>5 million) across many racial, ethnic and socioeconomic strata and collectively perform more than 4000 TKA procedures per year. The overall project goal of the proposed research study is to provide high fidelity clinical, biological and psychological data in conjunction with Clinical Coordination Center, the Data Integration and Resource Center, and the Omics Data Generation Center from patients undergoing TKA within our NCATS CTSA-funded program hub in line with NIH HEAL Initiative A2CPS. This information should enrich our understanding of how acute pain becomes chronic pain following surgery and enhance our ability to target effective preventive and treatment strategies for patients.