SUMMARY The importance of biomarkers in clinical practice and regulatory science is difficult to overstate. The ultimate goal for clinical care of the future is to determine the most appropriate therapy for each patient’s unique version of a particular disease. This concept of precision medicine has been identified as a national priority in the USA, leading to a need for biomarkers that can provide objective and reproducible information. In addition, regulatory science for the approval of new qualified drugs and medical technologies has an urgent need for qualified biomarkers to report on the success or failure of these drugs and technologies. Imaging biomarkers, providing in situ “biopsies”, have the potential to provide such specific information and, ultimately, to improve routine clinical care and speed up development of new treatments. The overall goal of this Resource therefore is to develop novel noninvasive MRI candidate biomarkers that can ultimately be used for: (i) personalized assessment of patients for diagnosis, prognosis, and treatment monitoring; (ii) monitoring of the development of new medical technologies and drugs, i.e. for better guiding of clinical trials. The significance of our proposed developments lies in providing the fundamental design and initial testing (i.e. not clinical trials itself) of new MRI candidate biomarkers with the potential to provide surrogate quantitative imaging endpoints that are as close as possible to clinical endpoints. As such, this Resource will focus on designing, calibrating and standardizing new magnetic resonance (MR) technologies to provide reliable measures across sessions, scanners, and raters. This technology will then be disseminated for larger scale patient studies to allow clinical validation. The MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers is an interdepartmental and interdisciplinary consortium combining facilities and expertise of the F.M. Kirby Research Center at Kennedy Krieger Institute (KKI), the Department of Radiology at Johns Hopkins University (JHU) School of Medicine, the Center for Imaging Science at the JHU Whiting School of Engineering, and the Department of Biostatistics at the JHU Bloomberg School of Public Health. We propose 4 TRD projects, 3 on MR acquisition approaches and one bringing them together with advanced multi-scale data analysis methods that include machine learning. To assure a proper choice of technologies, we will interact closely with a group of clinical and research experts in a push-pull relationship through collaborative projects (CPs) that focus on brain diseases, disorders, and injuries that have a need for new quantitative MR technology to better and noninvasively assess them. These include anemia/ischemia and related white matter hyperintensity lesions (CPs 1,5), aging, cerebrovascular disease, and dementia (CPs 2,7,10), traumatic brain injury (CP4), glymphatic function (CP6), pain (CP8) and addiction (CP9). As an initial testbed for our methods, we also have a group of service projects (SPs) to which we will provide both data acquisition methods and data analysis software. Finally, we will train investigators in their use and disseminate methods nationwide and to MRI manufacturers for even broader application.

Narrative The MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers is an interdepartmental and interdisciplinary consortium combining facilities and expertise of multiple departments and schools at the Kennedy Krieger Institute and the Johns Hopkins University. The goal of this National Center is to develop novel noninvasive MRI candidate biomarkers that can ultimately be used for (i) personalized assessment of patients for diagnosis, prognosis, and treatment monitoring (Precision Medicine), and (ii) expediting the development of new medical technologies and drugs. We will provide training in these new advanced technologies, and disseminate them to other research centers and hospitals in the country and worldwide.