Toxicity to the hematopoeitically active bone marrow (BM) is generally dose-limiting for patients undergoing radionuclide therapy without a prior stem cell support. The goal of radionuclide therapy is thus to provide sufficient cell kill to the targeted tumor, while sparing normal tissues such as the bone marrow, lungs, and kidneys. The effectiveness of the therapy therefore depends on the accuracy of the BM dose estimate and the use of that estimate in clincial trials for developing predictive dose-response models of marrow toxicity. BM absorbed dose is estimated using the MIRD schema, which requires in some cases explicit knowledge of the total mass of BM in a given patient, a parameter which cannot be readily measured. In response to this need, we have recently developed a regression model that allows for the prediction of BM mass in a given patient using only simply measurements of coaxed width and height taken from a pelvic CT or even radiograph image. However, the model is partially based on the use of standardized reference values bone marrow cellularity data from the radiation protection literature, data that was compiled from various and incongruent studies and which are partially based on unclear or questionable methodologies. In addition, the marrow cellularity data provided by the International Commission on Radiological Protection (ICRP) does not allow for adequate sex and age discrimination, or the 'assessment of uncertainties. That cellularity changes with age and that there are differences in males and females has been well documented in the literature, and hence should be taken into account. The current gold standard for measuring marrow cellularity is a painful and highly invasive BM biopsy of the iliac crest. This measure is unreliable, since cellularity is likely to be bone-site dependent and the volume sampled in a typical biopsy is very small. Magnetic resonance imaging (MRI) and spectroscopy (MRS) methods have been demonstrated as non- invasive means for measuring BM cellularity in patients. Their accuracy has been demonstrated in phantom studies and in vivo for the iliac bone, lumbar vertebrae, femoral head, and proximal end of the tibia. We propose a study in which we will use MRS on a clinical 3T scanner to expand cellularity measurements to the thirteen bone sites identified in ICRP Publication 70 to contain active BM in adults. The technique will be first validated using lipid/water phantoms and then in vivo by comparing MRS and histology measurements on amputated canine limbs followed by whole skeletal measurements. Finally, a human volunteer study will provide the cellularity values needed to improve the accuracy of our predictive model for BM mass in human adults for use in radionuclide therapy and in other clinical areas.
|Pichardo, Jose C; Milner, Rowan J; Bolch, Wesley E (2011) MRI measurement of bone marrow cellularity for radiation dosimetry. J Nucl Med 52:1482-9|