Bone marrow dosimetry via microCT imaging and stem cell spatial mapping

In order to make predictions of radiation dose in patients undergoing targeted radionuclide therapy of cancer, an accurate model of skeletal tissues is necessary. Concerning these tissues, the dose-limiting factor in these therapies is the toxicity of the hematopoietically active bone marrow. In addition to acute effects, one must be concerned as well with long-term stochastic effects such as radiation-induced leukemia. Particular cells of interest for both toxicity and cancer risk are the hematopoietic stem cells (HSC), found within the active marrow regions of the skeleton. At present, cellular-level dosimetry models are complex, and thus we cannot model individual stem cells in an anatomic model of the patient. As a result, one reverts to looking at larger tissue regions where these cell populations may reside.;To provide a more accurate marrow dose assessment, the skeletal dosimetry model must also be patient-specific. That is, it should be designed to match as closely as possible to the patient undergoing treatment. Absorbed dose estimates then can be tailored based on the skeletal size and trabecular microstructure of an individual for an accurate prediction of marrow toxicity. Thus, not only is it important to accurately model the target tissues of interest in a normal patient, it is important to do so for differing levels of marrow health.;A skeletal dosimetry model for the adult female was provided for better predictions of marrow toxicity in patients undergoing radionuclide therapy. This work is the first fully established gender specific model for these applications, and supersedes previous models in scalability of the skeleton and radiation transport methods. Furthermore, the applicability of using bone marrow biopsies was deemed sufficient in prediction of bone marrow health, specifically for the hematopoietic stem cell population. The location and concentration of the HSC in bone marrow was found to follow a spatial gradient from the bone trabeculae in lymphoma patients. Interestingly, chemotherapy was not found to effect the HSC population in concentration or gradient. Together, this work will provide more realistic and accurate dosimetry in internal radiation therapy of cancer patients.