Congratulations to Dr. Wesley Bolch, Distinguished Professor, Dr. John Aris, Associate Professor, and their collaborators on their $8.1M award from the Department of Defense, Peer Reviewed Medical Research Program (PRMRP) titled, Aligning Dosimetry and Biomarkers of Lung Injury with Prophylaxis and Mitigation of Damage from Radionuclides and Metals.

A team of investigators at the University of Florida, Northwestern University, and collaborating institutions with a shared interest in the evaluation of radionuclide contamination through new approaches to dosimetry and mitigation strategies will address challenges in the preservation of lung health in active duty service members, Veterans, military beneficiaries, and/or the American public with high-levels of a radionuclide or toxic metal environmental contamination following exposure of events.

This proposal addresses four topic areas:

• Pulmonary Fibrosis
• Respiratory Health
• Metals Toxicology (of the lung)
• Sustained Release Drug Delivery

From six different institutions:

• Northwestern University
• University of Florida
• University of California, Berkeley National Laboratory
• Georgia Institute of Technology
• Oak Ridge Associated University
• Oak Ridge National Laboratory

There are many instances for which active members of the U.S. military, including military service personnel and Warfighters, might be deployed to areas that are heavily contaminated with airborne or ground-dispersed radionuclides. These exposure scenarios might follow terrorist-type activities to include the detonation of either a radiological dispersion device (RDD) or improved nuclear devices (IND), or the sabotage of nuclear power plant stations (NPP) or industrial facilities. While civilian agencies and personnel will be deployed in a first-responder capacity, the U.S. military will most assuredly be called upon to assist.

Response of lungs to such exposures will define many of the subsequent health outcomes – from acute pulmonary distress and death to long term fibrosis injury, the effects of which may lead to debilitation many months or even years after exposure.

Findings from the proposed study will enable military decision makers to predict the most likely outcomes of specific exposures and provide means for the military to count on a specific level of pulmonary health among the exposed personnel.

This project will harness expertise from a group of experts with complementary expertise in radiation dosimetry, radiochemistry, measurement science, radiation transport modeling, computational fluid particle dynamics, chemical elemental mapping at both the tissue and cellular level, biomarkers discovery associated with different exposures and degrees of injury, as well as development of long-term sustained release agents with prophylactic properties to mitigate the injury. Data provided by the software readout will also link inhalation exposure with the predictions of subsequent physiological processes leading to lung damage and systemic damage.

Pre-clinical studies in this proposal may enable future interventions that would modulate the degree of lung injury prophylactically or after the exposure. This proposal seeks to create soft tissue phantoms, field-assessment software and hardware, mitigation agents, and biomarkers for exposure for military personnel.

Bolch will serve as Principal Investigator for Thrust Area 1 of the DoD PRMRP consortium, which seeks to develop deployable software for rapid assessment of lung dose following RDD/IND/NW events. He will provide overall guidance in all aspects of the study, including the design of lung vascular models and phantom library development within Aim 1, Monte Carlo radiation transport design under Aims 2 and 4, and overall software design under Aim 3. Aris will take primary responsibility for all-optical imaging of the tissue histology sections for each of the three tissues of focus in Aim 5.

Bolch and Aris’ hypothesis that improved anatomical models of the lungs can provide a more meaningful platform for lung dosimetry as relevant to the prediction of radiation-induced lung injury.

The team’s objective is to use these enhanced anatomic models to design in-field assessment software tools and associated hardware for radiological triage of RDD and IND contaminated Warfighters and other military personnel following inhalation of radionuclides or radionuclide mixtures.

Short-term impact: (1) provide the U.S. military with a rapid and field-deployable means of interpreting hand-held survey meter count rates in terms of radiation dose received to the lung tissues and to other organs of concern in acute internal radiation exposures, and (2) provide the U.S. military with lung tissue dosimetry following radionuclide intakes at the cellular level in a manner that accounts for the spatial non-uniformity of the decay sites, and considered target cells thought to be responsible for both acute and chronic lung injury.

Long-term impact: (1) provide the U.S. military and the broader scientific community with a new array of mesh-based computational phantoms with detailed models of the pulmonary airways and blood vasculature. (2) provide the U.S. military and the broader-scientific community with cellular-level models of the lung tissues. These models can additionally be used to study cellular-based lung dosimetry in radiopharmaceutical therapies and inhalation drug therapies for a variety of medical conditions.

The project will advance radiation biology into the realm of incidental radionuclide exposures. It will advance the ability to assist military personnel exposed to lung injury from radionuclides and metal particulates.

TEAM MEMBERS:

TA1:

• Wesley Bolch, Ph.D., Distinguished Professor, Department of Biomedical Engineering, University of Florida, will serve as PI for Thrust Area 1 and Deputy Director of the entire Program.
• John Aris, Ph.D., Associate Professor, Department of Anatomy and Cell Biology, University of Florida, a noted cell biologist and histologist, whose library of histological images will be used in the construction of novel 3D mesh-based cellular-level lung models for radiation dose assessment.

TA2:

• Shaheen Dewji, Ph.D., Assistant Professor, Nuclear Engineering Program, Georgia Institute of Technology

TA3:

• Gayle E Woloschak, Ph.D., project PI, Associate Dean for Graduate Student and Postdoctoral Affairs, Professor, Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University
• Tatjana Paunesku, Ph.D., Associate Professor for Research, Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University

TA4:

• Rebecca Abergel, PhD., (PI), Assistant Professor, Nuclear Engineering, University of California Berkley

Core:

• David Hooper, Nuclear Forensics and Consequence Management R&D, Oak Ridge National Laboratory
• Ashley Golden, Biostatistician, Oak Ridge National Laboratory
• Jason Davis, Internal Dosimetrist and Radiation