NIH grant to develop methods to quantify the interaction of radiation with the immune system

Wesley Bolch, Ph.D.

A $2.5M NIH National Cancer Institute grant has been funded over a five-year period to the University of Florida J. Crayton Pruitt Department of Biomedical Engineering and Massachusetts General Hospital (MGH) to develop methods to quantify the interaction of radiation with the immune system.

UF BME distinguished professor, Dr. Wesley Bolch, is dual PI with professor of radiation oncology at MGH, Dr. Harold Paganetti. The project aim is to provide the modeling tools necessary to compute the distribution of radiation dose to circulating lymphocytes during external beam radiotherapy – by either photons or protons – and thus treat these important immune cells as another “organ-at-risk” whose dose should be minimized through treatment optimization.

Clinical data indicate that patients with severe lymphopenia following a course of radiotherapy have significantly poorer long-term outcomes than patients with normal blood cell counts. Clinicians routinely design radiotherapy treatment plans to avoid doses exceeding toxicity thresholds for many organs such as the optic nerve, bone marrow, and kidneys.

There are currently no whole-body computational human phantoms available to facilitate the calculation of blood or lymphocyte dose-volume histograms. The phantoms to be developed in this study will be the first to fill this urgent need for radiation therapy and research communities. In addition to the overall innovative nature of this project, several of their methods are novel and have never been employed in radiation oncology:

  • The first use of tetrahedral mesh structures to model blood vessels (Aim 1)
  • The first implementation of a whole-body compartment model for blood flow (Aim 2)
  • The first four-dimensional modeling of blood flow using vasculature structures (Aim 3)
  • The first model of the mouse vasculature for pre-clinical studies (Aim 4)

Bolch’s laboratory will provide detailed enhancements to polygon-mesh based computational phantoms of the average sized adult and adolescent male and female patients to include anatomically realistic models of intra-organ vasculature. UF BME professor and study co-investigator, Dr. Peter McFetridge, will be responsible for developing detailed models of the blood vasculature in the laboratory mouse to include major vessels and intra-organ vessels via vascular corrosion casting techniques.

Bolch is the Director of the University of Florida’s Advanced Laboratory for Radiation.

Dosimetry Studies – ALRADS. The primary focus of the laboratory over the past decade has been the development of 3D anatomic models of patients for both retrospective and prospective assessment of radiation dose and associated cancer risk associated with diagnostic imaging and radiation therapies. Related studies include the development of patient-specific models of skeletal dosimetry based upon microCT imaging of bone and paired-image radiation transport.

The team envisions that future treatment planning in radiation oncology will treat lymphatic nodes and circulating blood cells as organs at risk and include them in the treatment planning process to minimize their radiation dose through particle type, dose rate, and beam delivery optimization.