Dartmouth Physically-Based Biodosimetry Center for Medical Countermeasures against Radiation

Physically-Based Biodosimetry for Triage after a Large Radiation Incident
Principal Investigator: Harold M. Swartz, M.D., Ph.D., M.P.H.

Overview [back to top]

The Dartmouth Physically-Based Biodosimetry Center for Medical Countermeasures against Radiation (Dart-Dose CMCR) is one of seven centers established by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) in 2010 to detect and counter radiation exposure in individuals. More information on the program can be found on the NIAID CMCR website.

The Dart-Dose CMCR is focused on the development of field deployable physical biodosimetry utilizing EPR measurements of teeth and nails through three synergistic projects and highly integrated cores based on prior progress. The rationale for our approach we believe is compelling, though relatively simple:

  1. In order to respond adequately to a radiation incident in which large numbers of individuals potentially have received doses of radiation that could lead to the acute radiation syndrome it is essential to determine the dose to individuals rapidly and accurately.
  2. The current capabilities and guidelines are not adequate for doing this.
  3. The dosimetry system should be based on radiation induced changes within the individual so that a “dosimeter” is always in place, i.e. biodosimetry is needed.
  4. Biologically based biodosimetry, while potentially very valuable, inherently must have ambiguity because it depends on the activation of responses to injury that are not specific for ionizing radiation, must vary in time as the responses are developed and later attenuated, and are very likely to be affected by both pre-existing conditions and concurrent perturbations such as stress, wounds, and burns.
  5. Physical biodosimetry does not have the potential limitations of the biologically based biodosimetry.
  6. EPR dosimetry based on radiation-induced changes in teeth and nails is the most advanced physical biodosimetric technique and has been shown to be capable of resolving doses in the range of interest with immediate readout.
  7. Our group has led the development of such EPR dosimetry and is poised to make it into a field deployable technique that can be implemented by non-expert operators without any prior training.

We will complete the development of the techniques and construct field-deployable prototypes of instruments based on three different and complimentary approaches: measurements in vivo in teeth, measurements in vivo in nails, and measurements in vitro on clipped fingernails. We expect these applications to be part of a multimodality approach to field dosimetry, complementing biological biodosimetry. We have potential commercial partners, especially General Electric, who is prepared to use the prototypes to carry out rapid FDA-compliable production of fully deployable versions as soon as the prototypes are available from the proposed center.

More information on the Projects and Cores [back to top]

Projects:

  • Project 1 - Biodosimetry based on EPR Measurements of Teeth In Vivo
  • Project 2 - Ex Vivo Analysis of Irradiated Finger/Toe Nails as a Biodosimeter System
  • Project 3 - Biodosimetry based on EPR Measurements of Nails In Vivo

Cores:

  • Core A - Scientific and Administrative Core
  • Core B - Pilot Project Core
  • Core C - In Vivo Irradiations with Patients Undergoling Radiation Therapy
  • Core D - Advanced Instrumental Development Core
  • Core E - Instrumental Core

Key Leaders for Dart-Dose CMCR [back to top]

Harold M. Swartz, M.D., Ph.D., M.P.H. - Expert in Clinical Applications of EPR [back to top]

Dr. Swartz is the PI and Director of the Dart-Dose CMCR and Project PI of Project 3, in vivo nail dosimetry, and Core Director on Core A. He is Professor of Radiology, Physiology, Community and Family Medicine, and The Dartmouth Institute (TDI) at Dartmouth Medical School (DMS) and Adjunct Professor of Chemistry (Dartmouth College) and Bioengineering (Thayer School of Engineering at Dartmouth). Dr. Swartz is considered by many to be the world’s leader in the biomedical applications of EPR, especially clinical applications and in vivo EPR spectroscopy. He published the first papers (in 1965 and 1968) that indicated the potential of EPR dosimetry for after-the-fact measurement of radiation dose. He has more than 450 publications, including more than 200 on in vivo EPR and EPR dosimetry. He established and continues to direct the EPR Center for the Study of Viable Systems at Dartmouth Medical School. He previously established and directed EPR centers at the Medical College of Wisconsin (with Dr. Hyde) and at the University of Illinois at Urbana-Champaign and serves on three Advisory Boards for EPR centers. He has received several medals and the Zavoisky Award for his accomplishments in biological applications of EPR and has 6 patents in this field.

Ann Barry Flood, Ph.D. - Organizational Sociologist/Health Policy Expert [back to top]

Dr. Flood is the Core Director of the Pilot Projects Core (Core B) and a Associate Director of the CMCR. She is Professor of Community and Family Medicine, Radiology and The Dartmouth Institute for Health Policy and Clinical Practice (TDI) at Dartmouth Medical School and Adjunct Professor of Sociology at Dartmouth College. She chaired the Ph.D. Program and the Postdoctoral Program at TDI for 15 years and has been a co-Editor-in- Chief of Health Services Research, the leading US journal for this type of research, since 2002. She is an expert on survey and outcomes research methods and in health policy, quality, costs and quality improvement and decision-making in teams and health care systems, and sustainability of interventions and dissemination and payment systems for health care technologies.

Eva C. Guinan, M.D. - Hematologist/Oncologist/Pediatrician [back to top]

Dr. Guinan is the Core Director of Core C at Dana-Farber Cancer Institute (DFCI) for the proposed CMCR at Dartmouth. She is an Associate Professor of Pediatrics at Harvard Medical School and a member of the Department of Pediatric Oncology, which is located the DFCI/Children’s Hospital Cancer Care. She is a clinical investigator with over 25 years of experience in myeloablative hematopoietic stem cell transplantation. She has published widely in the area of transplant conditioning mediated toxicity and also studies the impact of genetic makeup on risk for regimen-related toxicity during transplantation and the development of novel agents for prevention or treatment of regimen-related toxicity.

James S. Hyde, Ph.D. - EPR Instrumental Expert [back to top]

Dr. Hyde, the James S. Hyde Professor of Biophysics at the Medical College of Wisconsin (MCW) and the Core Director of Core D, is the co-founder (along with Harold Swartz) and current Director of the National Biomedical EPR Center located MCW. He is internationally recognized as the leading expert in EPR instrumentation and MRI technologies and applications is also founder and President of a company manufacturing EPR instrumental accessories. Dr. Hyde’s work in EPR and MRI has ongoing implications for research and health care in many fields including radiology, neurology, plastic surgery, gastroenterology and ophthalmology. Dr. Hyde has published more than 370 articles in medical and physical science peer-reviewed journals. He has secured 33 U.S. patents in imaging and EPR technology. He led the Medical College’s interdisciplinary team that was among the first in the world to develop functional MRI (fMRI) of the working brain. He has been awarded numerous national and international gold medals and the Zavoisky medal for his work.

Piotr Lesniewski, M.S.E. - Hardware Engineer [back to top]

Mr. Lesniewski is the Core Director of the Instrumental Core (Core E) of the proposed CMCR at Dartmouth. Mr. Lesniewski is a world–recognized leading expert in the development of EPR hardware, including resonators for uses in human subjects. He has extensive experience and successes in resonator development, especially L-Band resonators and extensive experience and achievements in the development of microwave bridges, especially L-Band bridges. He is currently the Associate Director for Instrumental Developments in the EPR Center at Dartmouth, where he has worked with distinction for more than 15 years.

Steven Swarts, Ph.D. - Analytical Chemist [back to top]

Dr. Swarts will be the Project PI for Project 2, in vitro nail dosimetry, for the CMCR at Dartmouth. He is an analytical chemist with 28 years of experience in the development and validation of instrument-based qualitative and quantitative methods. This experience has included the development and application of EPR, liquid chromatography (HPLC and LC-MS), and gas chromatography (GC-MS) based analytical methods for the detection and quantification of free radicals and their end-products. He has extensive research experience in the radiation chemistry of biomolecules, including DNA and proteins, especially in solid state systems. Dr. Swarts has conducted research over the past 2+ years on the use of ex vivo EPR measurements in nails under a pilot grant from the University of Rochester CMCR and in a collaborative effort with Dr. Swartz and his research team at Dartmouth. Dr. Swarts will continue and expand this research at the University of Florida after moving there in July 2010. His experience in method development and validation will also help in evaluating methods to minimize the influence of these sources of variability on nail measurements.

Benjamin B. Williams, Ph.D. - Medical Physicist [back to top]

Dr. Williams is the Project PI of Project 1, the tooth dosimetry project, and Associate Director of the CMCR at Dartmouth. Currently he is the Associate Director for the EPR Center at Dartmouth with responsibilities for Biological Applications. He is Research Assistant Professor in the Department of Radiology at Dartmouth Medical School (DMS). His Ph.D. dissertation was on in vivo EPR. He has received several awards in recognition of his scientific excellence in EPR clinical applications including the Forbeck Scholar Award, EPR International Conference Young Investigator Award, and the Bernard Smaller Prize for Magnetic Resonance Research. His peer-reviewed publications include work in both EPR oximetry as well as dosimetry, and his experimental work includes work in both human and animal models.

Internal Advisory Committee for Dart-Dose CMCR [back to top]

  • Denise Anthony, Ph.D.
  • Robert M. Gougelet, M.D.
  • Alan Charles Hartford, M.D., Ph.D.
  • Mark A. Israel, M.D.
  • Adam M. Keller, M.P.H.
  • David Kotz, Ph.D.
  • Keith D. Paulsen, Ph.D.
  • Joseph M. Rosen, M.D.
  • Wiley Souba, M.D., Sc.D., M.B.A.
  • Peter K. Spiegel, M.D.
  • John B. Weaver, Ph.D.

External Advisory Committee for Dart-Dose CMCR [back to top]

  • Murali Cherukuri, Ph.D. (National Cancer Institute)
  • Gareth Eaton, Ph.D. (University of Denver)
  • Wojchiech Froncisz, Ph.D. (Jagiellonian University)
  • Howard Halpern, M.D., Ph.D. (University of Chicago)
  • Terry Pellmar, Ph.D. (Applied Research Associates, Inc.)
  • Fraser Robb, Ph.D. (GE)