MAGNETIC RESONANCE STUDIES OF BONE MARROW HEMATOPOIESIS

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The goals of the proposed work are to develop a non-invasive assay for characterizing hematopoieitic activity in human bone marrow, and to test its utility in monitoring and staging patients with hematologic malignancies. Presently, the needle aspirate and biopsy are used for definitive diagnosis and therapeutic monitoring. In addition to causing patient discomfort, biopsies and aspirates are limited to superficial areas of bone, such as the posterior iliac crest. The proposed assay will be designed to complement information obtained from the needle biopsy by providing a measure of the spatial extent of disease, particularly at sites inaccessible to the needle biopsy. The technical goals of the project are concerned with the development of recently introduced magnetic resonance bone marrow scanning technology. It was demonstrated that nearly complete segmentation of leukemic bone marrow was possible using a high speed magnetic resonance imaging protocol with contrast based in part upon the self-diffusion coefficient of intracellular versus extracellular water. Furthermore, the quality of the segmentation was high enough to facilitate a projection scan approach which allows a rapid assessment of extent of disease. Earlier studies of the bone marrow by magnetic resonance could not definitively detect leukemic infiltration, but rather measured changes related to bone marrow cellularity. The present effect appears to specifically screen for abnormal cells in acute lymphocytic leukemia. The research plan includes studies to 1) improve the sensitivity of the method, 2) determine the range of hematologic pathologies where it is applicable, and 3) assess its utility for patient management. Patient populations will include acute and chronic leukemia, lymphoma, multiple myeloma, and myelodysplastic syndrome. The utility of the methods will be assessed in 1) monitoring therapeutic efficacy in acute and chronic leukemia, lymphoma, and multiple myeloma, and 2) staging in chronic leukemia, lymphoma, and myelodysplastic syndrome.